Case#: Case 2, proband was an 2-year-old female of Mexican origin. She was born at full term via cesarian section at 7 lbs and 6 oz.

DiseaseAssertion: MPS1-H

FamilyInfo: Proband came from a consanguineous union (uncle-niece). Case 1 is the proband's brother.

CasePresentingHPOs: Recurrent otitis media (HP:0000403)

CaseHPOFreeText: She also had more than 10 ear infections, and was diagnosed with bilateral moderate to severe hearing loss. She was mildly delayed, mainly in language.

CaseNotHPOs: N/A

CaseNotHPOFreeText: Her physical growth was not impaired.

CaseEnzymeAssay: N/A

CaseUrineGAGs: N/A

CaseERT: Given the conclusion to discontinue enzyme replacement therapy in her brother, the decision was made, again with the participation of the patient's mother, not to initiate ERT unless she developed somatic symptoms that could be alleviated with treatment.

CaseBMT: N/A

Variant1: c.923T>C (p.L308P)

Variant1ClinVarID: 502243

Variant1CAID: CA2802119

Variant2: c.923T>C (p.L308P)

Variant2ClinVarID: 502243

Variant2CAID: CA2802119

AdditionalVariants: Shee also had a homozygous variant (c.268G>A) in the SGSH gene, and additionally diagnosed with Sanfilippo syndrome type A.

ParentalGenotype: N/A

PreviouslyPublished N/A

Case#: Case 1, proband was an 8-year-old male of Mexican origin. He was born at 32 weeks gestational age; 3 lbs and 12 oz. He was diagnosed at 1.5 years old.

DiseaseAssertion: MPS1-H

FamilyInfo: Proband came from a consanguineous union (uncle-niece). Case 2 is the proband's sister.

CasePresentingHPOs: Developmental delay, coarse facial features, gastroesophageal reflux, hiatal hernia, umbilical hernia, recurrent otitis media, hepatomegaly, dysostosis multiplex, joint stiffness (HP:0001263, HP:0000280, HP:0002020, HP:0002036, HP:0001537, HP:0000403, HP:0002240, HP:0000943, HP:0001387)

CaseHPOFreeText: He had bilateral moderate to severe hearing loss. He had a normal ophthalmologic examination at 3 years of age, and at age 8 has not developed corneal clouding. He had contractures at the knees as well.

CaseNotHPOs: N/A

CaseNotHPOFreeText: N/A

CaseEnzymeAssay: Enzyme analysis on fibroblasts showed 10% residual alpha-l-iduronidase activity and no detectable activity for heparan N-sulfatase.

CaseUrineGAGs: Urinary quantitation of glycosaminoglycans showed 127 mg/g creatinine of uronic acid by the orcinol reaction (nl. 10.7 ± 8.0) and 449 mg/g creatinine by the carbazole reaction (nl. 16.9 ± 9.9), giving a carbazole to orcinol ratio of almost 3, which is indicative of excess heparan sulfate as compared with dermatan sulfate. The electrophoresis which revealed a strong band of heparan sulfate and slightly less chondroitin sulfate was confirmatory of this conclusion. N-sulfated hexosamine was 126 mg/g creatinine (nl. 15.8 ± 12).

CaseERT: He was started on enzyme replacement therapy (ERT) for iduronidase deficiency at age 3 years. However, his severe hyperactivity often precluded therapy as he could not sit still during the infusions, and the intravenous access catheter infiltrated on numerous occasions. Given his mild somatic symptoms, the concurrent diagnosis of Sanfilippo syndrome, a lethal condition, as well as the difficulty his family had with his complex medical care, the decision was made with the family's participation and accord to discontinue ERT and to treat only those problems that would improve his quality of life. He was on ERT for a total of 3 years.

CaseBMT: He was evaluated for a bone marrow transplant but was determined to be ineligible due to his low developmental quotient.

Variant1: c.923T>C (p.L308P)

Variant1ClinVarID: 502243

Variant1CAID: CA2802119

Variant2: c.923T>C (p.L308P)

Variant2ClinVarID: 502243

Variant2CAID: CA2802119

AdditionalVariants: He also had a homozygous variant (c.268G>A) in the SGSH gene, and additionally diagnosed with Sanfilippo syndrome type A.

ParentalGenotype: N/A

PreviouslyPublished N/A

Case#: Patient 50, male, Han origin, 5 years 6 months old (age at diagnosis)

DiseaseAssertion: MPS1-H/S

FamilyInfo: N/A

CasePresentingHPOs: Macrocephaly, Joint stiffness, Hepatosplenomegaly, Hernia, Airway obstruction (HP:0000256, HP:0001387, HP:0001433, HP:0100790, HP:0006536)

CaseHPOFreeText: N/A

CaseNotHPOs: Global Developmental Delay, Mongolian macula (HP:0001263, HP:0011369)

CaseNotHPOFreeText: Cardiac disease

CaseEnzymeAssay: IDUA activity 0.8 nmol/h/mg protein. The normal range in Chinese controls was found to be 27.2–52 nmol/h/mg protein.

CaseUrineGAGs: Diagnosis was confirmed biochemically by the demonstration of an increased excretion of urinary dermatan sulfate and heparan sulfate.

CaseERT: N/A

CaseBMT: N/A

Variant1: c.1898C>T (p.S633L)

Variant1ClinVarID: 556406

Variant1CAID: CA355966010

Variant2: N/A

Variant2ClinVarID: N/A

Variant2CAID: N/A

AdditionalVariants: N/A

ParentalGenotype: N/A

PreviouslyPublished N/A

Case#: Patient 55, female, Han origin, 2 years 3 months old (age at diagnosis)

DiseaseAssertion: MPS1-H/S

FamilyInfo: N/A

CasePresentingHPOs: Global Developmental Delay, Macrocephaly, Joint stiffness, Hepatosplenomegaly (HP:0001263, HP:0000256, HP:0001387, HP:0001433)

CaseHPOFreeText: Cardiac disease

CaseNotHPOs: Mongolian macula, Hernia, Airway obstruction (HP:0011369, HP:0100790, HP:0006536)

CaseNotHPOFreeText: N/A

CaseEnzymeAssay: IDUA activity 1.0 nmol/h/mg protein. The normal range in Chinese controls was found to be 27.2–52 nmol/h/mg protein.

CaseUrineGAGs: Diagnosis was confirmed biochemically by the demonstration of an increased excretion of urinary dermatan sulfate and heparan sulfate.

CaseERT: N/A

CaseBMT: N/A

Variant1: c.236C>T (p.A79V)

Variant1ClinVarID: 1458769

Variant1CAID: CA356987

Variant2: c.503G>T (p.G168V)

Variant2ClinVarID: 4069658

Variant2CAID: CA355961655

AdditionalVariants: N/A

ParentalGenotype: The transmission of sequence variations found in each patient was inferred by sequencing the corresponding exons of the patient's parents - confirmed in trans by parental testing.

PreviouslyPublished N/A

Case#: Patient 42, male, Han origin, 2 years old (age at diagnosis)

DiseaseAssertion: MPS1-H

FamilyInfo: N/A

CasePresentingHPOs: Global Developmental Delay, Macrocephaly, Joint stiffness, Mongolian macula, Hepatosplenomegaly, Hernia (HP:0001263, HP:0000256, HP:0001387, HP:0011369, HP:0001433, HP:0100790)

CaseHPOFreeText: Cardiac disease

CaseNotHPOs: Airway obstruction (HP:0006536)

CaseNotHPOFreeText: N/A

CaseEnzymeAssay: IDUA activity 1.0 nmol/h/mg protein. The normal range in Chinese controls was found to be 27.2–52 nmol/h/mg protein.

CaseUrineGAGs: Diagnosis was confirmed biochemically by the demonstration of an increased excretion of urinary dermatan sulfate and heparan sulfate.

CaseERT: N/A

CaseBMT: N/A

Variant1: c.1402+1G>T

Variant1ClinVarID: 1323099

Variant1CAID: CA355964387

Variant2: c.1402+1G>T

Variant2ClinVarID: 1323099

Variant2CAID: CA355964387

AdditionalVariants: N/A

ParentalGenotype: The transmission of sequence variations found in each patient was inferred by sequencing the corresponding exons of the patient's parents - confirmed by parental testing.

PreviouslyPublished N/A

Case#: Patient 26, female, Han origin, 3 years old (age at diagnosis)

DiseaseAssertion: MPS1-H

FamilyInfo: N/A

CasePresentingHPOs: Global Developmental Delay, Macrocephaly, Joint stiffness, Mongolian macula, Hepatosplenomegaly, Hernia, Airway obstruction (HP:0001263, HP:0000256, HP:0001387, HP:0011369, HP:0001433, HP:0100790, HP:0006536)

CaseHPOFreeText: Cardiac disease

CaseNotHPOs: N/A

CaseNotHPOFreeText: N/A

CaseEnzymeAssay: N/A

CaseUrineGAGs: Diagnosis was confirmed biochemically by the demonstration of an increased excretion of urinary dermatan sulfate and heparan sulfate.

CaseERT: N/A

CaseBMT: N/A

Variant1: 668insGCG, it looks like this should be c.665_667dup

Variant1ClinVarID: N/A

Variant1CAID: CA2586965942

Variant2: c.236C>T (p.A79V)

Variant2ClinVarID: 1458769

Variant2CAID: CA356987

AdditionalVariants: N/A

ParentalGenotype: The transmission of sequence variations found in each patient was inferred by sequencing the corresponding exons of the patient's parents - confirmed in trans by parental testing.

PreviouslyPublished N/A

Case#: Patient 24, male, Han origin, age not available

DiseaseAssertion: N/A

FamilyInfo: N/A

CasePresentingHPOs: N/A

CaseHPOFreeText: N/A

CaseNotHPOs: N/A

CaseNotHPOFreeText: N/A

CaseEnzymeAssay: IDUA activity 2.3 nmol/h/mg protein. The normal range in Chinese controls was found to be 27.2–52 nmol/h/mg protein.

CaseUrineGAGs: Diagnosis was confirmed biochemically by the demonstration of an increased excretion of urinary dermatan sulfate and heparan sulfate.

CaseERT: N/A

CaseBMT: N/A

Variant1: N/A

Variant1ClinVarID: N/A

Variant1CAID: N/A

Variant2: c.296+4G>A, it looks like this is a typo and should be c.299+4G>A

Variant2ClinVarID: N/A

Variant2CAID: CA2669476183

AdditionalVariants: N/A

ParentalGenotype: N/A

PreviouslyPublished N/A

Case#: Patient 10, female, Han origin, 2.5 years old (age at diagnosis)

DiseaseAssertion: MPS1-H

FamilyInfo: N/A

CasePresentingHPOs: Global Developmental Delay, Macrocephaly, Joint stiffness, Hepatosplenomegaly, Airway obstruction (HP:0001263, HP:0000256, HP:0001387, HP:0001433, HP:0006536)

CaseHPOFreeText: Cardiac disease

CaseNotHPOs: Mongolian macula, Hernia (HP:0011369, HP:0100790)

CaseNotHPOFreeText: N/A

CaseEnzymeAssay: IDUA activity 0.2 nmol/h/mg protein. The normal range in Chinese controls was found to be 27.2–52 nmol/h/mg protein.

CaseUrineGAGs: Diagnosis was confirmed biochemically by the demonstration of an increased excretion of urinary dermatan sulfate and heparan sulfate.

CaseERT: N/A

CaseBMT: N/A

Variant1: c.236C>T (p.A79V)

Variant1ClinVarID: 1458769

Variant1CAID: CA356987

Variant2: c.536C>G (p.T179R)

Variant2ClinVarID: 556358

Variant2CAID: CA355961718

AdditionalVariants: N/A

ParentalGenotype: Father - c.236C>T, Mother - c.536C>G. The transmission of sequence variations found in each patient was inferred by sequencing the corresponding exons of the patient's parents - confirmed in trans by parental testing.

PreviouslyPublished N/A

Case#: Patient 11, male, Han origin, 7 years old (age at diagnosis)

DiseaseAssertion: MPS1-H/S

FamilyInfo: N/A

CasePresentingHPOs: Macrocephaly, Joint stiffness, Hepatosplenomegaly, Hernia, Airway obstruction (HP:0000256, HP:0001387, HP:0001433, HP:0100790, HP:0006536)

CaseHPOFreeText: Cardiac disease

CaseNotHPOs: Global Developmental Delay, Mongolian macula (HP:0001263, HP:0011369)

CaseNotHPOFreeText: N/A

CaseEnzymeAssay: IDUA activity 0.1 nmol/h/mg protein. The normal range in Chinese controls was found to be 27.2–52 nmol/h/mg protein.

CaseUrineGAGs: Diagnosis was confirmed biochemically by the demonstration of an increased excretion of urinary dermatan sulfate and heparan sulfate.

CaseERT: N/A

CaseBMT: N/A

Variant1: c.236C>T (p.A79V)

Variant1ClinVarID: 1458769

Variant1CAID: CA234128

Variant2: c.236C>T (p.A79V)

Variant2ClinVarID: 1458769

Variant2CAID: CA234128

AdditionalVariants: N/A

ParentalGenotype: The transmission of sequence variations found in each patient was inferred by sequencing the corresponding exons of the patient's parents - confirmed by parental testing.

PreviouslyPublished N/A

Case#: Patient 12, female, Han origin, 13 years old (age at diagnosis)

DiseaseAssertion: MPS1-S

FamilyInfo: N/A

CasePresentingHPOs: Joint stiffness, Hepatosplenomegaly (HP:0001387, HP:0001433)

CaseHPOFreeText: Cardiac disease

CaseNotHPOs: Global Developmental Delay, Macrocephaly, Mongolian macula, Hernia, Airway obstruction (HP:0001263, HP:0000256, HP:0011369, HP:0100790, HP:0006536)

CaseNotHPOFreeText: N/A

CaseEnzymeAssay: IDUA activity 0.0 nmol/h/mg protein. The normal range in Chinese controls was found to be 27.2–52 nmol/h/mg protein.

CaseUrineGAGs: Diagnosis was confirmed biochemically by the demonstration of an increased excretion of urinary dermatan sulfate and heparan sulfate.

CaseERT: N/A

CaseBMT: N/A

Variant1: c.536C>G (p.S633L)

Variant1ClinVarID: 556406

Variant1CAID: CA355966010

Variant2: c.536C>G (p.S633L)

Variant2ClinVarID: 556406

Variant2CAID: CA355966010

AdditionalVariants: N/A

ParentalGenotype: Father - c.536C>G, Mother - c.536C>G. The transmission of sequence variations found in each patient was inferred by sequencing the corresponding exons of the patient's parents - confirmed by parental testing.

PreviouslyPublished N/A

Case#: Patient 7, female, Han origin, 7 years old (age at diagnosis)

DiseaseAssertion: MPS1-H/S

FamilyInfo: N/A

CasePresentingHPOs: Global Developmental Delay, Macrocephaly, Joint stiffness, Hepatosplenomegaly (HP:0001263, HP:0000256, HP:0001387, HP:0001433)

CaseHPOFreeText: Cardiac disease

CaseNotHPOs: Mongolian macula, Hernia, Airway obstruction (HP:0011369, HP:0100790, HP:0006536)

CaseNotHPOFreeText: N/A

CaseEnzymeAssay: IDUA activity 0.3 nmol/h/mg protein. The normal range in Chinese controls was found to be 27.2–52 nmol/h/mg protein.

CaseUrineGAGs: Diagnosis was confirmed biochemically by the demonstration of an increased excretion of urinary dermatan sulfate and heparan sulfate.

CaseERT: N/A

CaseBMT: N/A

Variant1: c.1227dupG (paper says c.1225dupC but according to the variant sequence this should be c.1227dupG - a known variant)

Variant1ClinVarID: 929237

Variant1CAID: CA1139658406

Variant2: c.236C>T (p.A79V)

Variant2ClinVarID: 1458769

Variant2CAID: CA356987

AdditionalVariants: N/A

ParentalGenotype: The transmission of sequence variations found in each patient was inferred by sequencing the corresponding exons of the patient's parents - confirmed in trans by parental testing.

PreviouslyPublished N/A

Case#: Patient 34, male, Han origin, 10 months old (age at diagnosis)

DiseaseAssertion: MPS1-H

FamilyInfo: N/A

CasePresentingHPOs: Global Developmental Delay, Macrocephaly, Joint stiffness, Mongolian macula, Hepatosplenomegaly, Hernia, Airway obstruction (HP:0001263, HP:0000256, HP:0001387, HP:0011369, HP:0001433, HP:0100790, HP:0006536)

CaseHPOFreeText: Cardiac disease

CaseNotHPOs: N/A

CaseNotHPOFreeText: N/A

CaseEnzymeAssay: IDUA activity 1.2 nmol/h/mg protein. The normal range in Chinese controls was found to be 27.2–52 nmol/h/mg protein.

CaseUrineGAGs: Diagnosis was confirmed biochemically by the demonstration of an increased excretion of urinary dermatan sulfate and heparan sulfate.

CaseERT: N/A

CaseBMT: N/A

Variant1: c.656dupG (Paper refers to the variant as c.657dupG, there is a typo in the article where all duplication variants are one base pair off)

Variant1ClinVarID: N/A

Variant1CAID: CA2586965940

Variant2: c.623G>A (p.G208D)

Variant2ClinVarID: 554590

Variant2CAID: CA355961948

AdditionalVariants: N/A

ParentalGenotype: The transmission of sequence variations found in each patient was inferred by sequencing the corresponding exons of the patient's parents - confirmed in trans by parental testing.

PreviouslyPublished N/A

Case#: Patient 44, male, Han origin, 21 years old (age at diagnosis)

DiseaseAssertion: MPS1-S

FamilyInfo: N/A

CasePresentingHPOs: Joint stiffness (HP:0001387)

CaseHPOFreeText: N/A

CaseNotHPOs: Global Developmental Delay, Macrocephaly, Mongolian macula, Hepatosplenomegaly, Hernia, Airway obstruction (HP:0001263, HP:0000256, HP:0011369, HP:0001433, HP:0100790, HP:0006536)

CaseNotHPOFreeText: Cardiac disease

CaseEnzymeAssay: IDUA activity 1.5 nmol/h/mg protein. The normal range in Chinese controls was found to be 27.2–52 nmol/h/mg protein.

CaseUrineGAGs: Diagnosis was confirmed biochemically by the demonstration of an increased excretion of urinary dermatan sulfate and heparan sulfate.

CaseERT: N/A

CaseBMT: N/A

Variant1: c.2T>C (p.Met1Thr)

Variant1ClinVarID: 639529

Variant1CAID: CA2801095

Variant2: c.1037T>G (p.L346R)

Variant2ClinVarID: 11927

Variant2CAID: CA256128

AdditionalVariants: N/A

ParentalGenotype: The transmission of sequence variations found in each patient was inferred by sequencing the corresponding exons of the patient's parents - confirmed in trans by parental testing.

PreviouslyPublished N/A

Case#: P1, male, 1.1 years (age at HCT - hematopoietic cell transplantation), 2 iPS colonies per 100,000 cells (KC)

DiseaseAssertion: MPS1-H

FamilyInfo: N/A

CasePresentingHPOs: N/A

CaseHPOFreeText: N/A

CaseNotHPOs: N/A

CaseNotHPOFreeText: N/A

CaseEnzymeAssay: N/A

CaseUrineGAGs: N/A

CaseERT: N/A

CaseBMT: Yes - Donor cells were received from KC, keratinocytes. Study was conducted 0.2 years after HCT.

Variant1: c.501C>G (p.Y167X)

Variant1ClinVarID: 92644

Variant1CAID: CA220511

Variant2: c.1205G>A (p.W402X)

Variant2ClinVarID: 11908

Variant2CAID: CA220498

AdditionalVariants: N/A

ParentalGenotype: N/A

PreviouslyPublished N/A

Case#: No additional case information provided

DiseaseAssertion: MPSI-H/S

FamilyInfo: N/A

CasePresentingHPOs: N/A

CaseHPOFreeText: N/A

CaseNotHPOs: N/A

CaseNotHPOFreeText: N/A

CaseEnzymeAssay: 0.07 umol/g hr, reference range 10–50 umol/g hr.

CaseUrineGAGs: N/A

CaseERT: N/A

CaseBMT: N/A

Variant1: c.536C>A (p.T179K)

Variant1ClinVarID: 2734636

Variant1CAID: CA355961717

Variant2: c.536C>A (p.T179K)

Variant2ClinVarID: 2734636

Variant2CAID: CA355961717

AdditionalVariants: N/A

ParentalGenotype: N/A

PreviouslyPublished N/A

Case#: No additional case information provided

DiseaseAssertion: Not specified

FamilyInfo: N/A

CasePresentingHPOs: N/A

CaseHPOFreeText: N/A

CaseNotHPOs: N/A

CaseNotHPOFreeText: N/A

CaseEnzymeAssay: Abnormal

CaseUrineGAGs: Normal

CaseERT: N/A

CaseBMT: N/A

Variant1: c.1054T>C (p.F352L)

Variant1ClinVarID: 2432790

Variant1CAID: CA2802178

Variant2: c.1112T>A (p.V371D)

Variant2ClinVarID: 1470032

Variant2CAID: CA355963356

AdditionalVariants: N/A

ParentalGenotype: N/A

PreviouslyPublished N/A

Case#: No additional case information provided

DiseaseAssertion: MPSI-H/S

FamilyInfo: N/A

CasePresentingHPOs: N/A

CaseHPOFreeText: N/A

CaseNotHPOs: N/A

CaseNotHPOFreeText: N/A

CaseEnzymeAssay: Abnormal

CaseUrineGAGs: Normal

CaseERT: N/A

CaseBMT: N/A

Variant1: c.1205G>A (p.W402X)

Variant1ClinVarID: 11909

Variant1CAID: CA220498

Variant2: c.1577T>C (p.L526P)

Variant2ClinVarID: 567566

Variant2CAID: CA2802300

AdditionalVariants: N/A

ParentalGenotype: N/A

PreviouslyPublished N/A

Case#: No additional case information provided.

DiseaseAssertion: Not specified

FamilyInfo: N/A

CasePresentingHPOs: N/A

CaseHPOFreeText: N/A

CaseNotHPOs: N/A

CaseNotHPOFreeText: N/A

CaseEnzymeAssay: Abnormal

CaseUrineGAGs: Normal

CaseERT: N/A

CaseBMT: N/A

Variant1: c.1042_1062dup

Variant1ClinVarID: 2432708

Variant1CAID: CA549264534

Variant2: c.986A>G

Variant2ClinVarID: N/A

Variant2CAID: CA2802157

AdditionalVariants: N/A

ParentalGenotype: N/A

PreviouslyPublished N/A

Case#: No additional case information provided

DiseaseAssertion: Not specified

FamilyInfo: N/A

CasePresentingHPOs: N/A

CaseHPOFreeText: N/A

CaseNotHPOs: N/A

CaseNotHPOFreeText: N/A

CaseEnzymeAssay: Abnormal

CaseUrineGAGs: Normal

CaseERT: N/A

CaseBMT: N/A

Variant1: c.1051G>A (p.A351T)

Variant1ClinVarID: 967585

Variant1CAID: CA2802176

Variant2: c.497G>C (p.R166T)

Variant2ClinVarID: 1388155

Variant2CAID: CA2801967

AdditionalVariants: N/A

ParentalGenotype: N/A

PreviouslyPublished N/A

Case#: No additional case information provided

DiseaseAssertion: Not specified

FamilyInfo: N/A

CasePresentingHPOs: N/A

CaseHPOFreeText: N/A

CaseNotHPOs: N/A

CaseNotHPOFreeText: N/A

CaseEnzymeAssay: Not performed

CaseUrineGAGs: Normal

CaseERT: N/A

CaseBMT: N/A

Variant1: c.53T>C (p.L18P)

Variant1ClinVarID: 193062

Variant1CAID: CA238566

Variant2: c.1651G>C (p.V551L)

Variant2ClinVarID: 1410776

Variant2CAID: CA2802341

AdditionalVariants: N/A

ParentalGenotype: N/A

PreviouslyPublished N/A

Case#: OS of sibship 2, male, 1.3 years old (age at diagnosis), 3.3 years old (age at ERT enrollment), 11.7 years (duration of ERT)

DiseaseAssertion: MPS1-HS

FamilyInfo: Affected female YS (YS of sibship 2)

CasePresentingHPOs: HP:0007957, HP:0000943, HP:0002828, HP:0002650 (Corneal opacity, dysostosis, joint contractures, scoliosis)

CaseHPOFreeText: Cardiac disease, mild organomegaly, learning difficulties, progression of musculoskeletal symptoms,

CaseNotHPOs: N/A

CaseNotHPOFreeText: N/A

CaseEnzymeAssay: N/A

CaseUrineGAGs: N/A

CaseERT: Yes - Motor development remained normal while learning difficulties present at onset of ERT persisted. After 5 years of ERT, showed significant scoliosis and other spinal deformities

CaseBMT: N/A

Variant1: c.1598C>G (p.P533R)

Variant1ClinVarID: 11910

Variant1CAID: CA256112

Variant2: c.1598C>G (p.P533R)

Variant2ClinVarID: 11910

Variant2CAID: CA256112

AdditionalVariants: N/A

ParentalGenotype: N/A

PreviouslyPublished N/A

Case#: OS of sibship 8, male, 6.8 years old (age at diagnosis), 7 years old (age at ERT enrollment), 6.0 years (duration of ERT)

DiseaseAssertion: MPS1-HS

FamilyInfo: Affected YS (YS of sibship 8)

CasePresentingHPOs: HP:0007957, HP:0000943, HP:0002828 (Corneal opacity, dysostosis, joint contracture)

CaseHPOFreeText: Cardiac disease

CaseNotHPOs: N/A

CaseNotHPOFreeText: N/A

CaseEnzymeAssay: N/A

CaseUrineGAGs: N/A

CaseERT: Yes - Had progression of cardiac symptoms at T2 and dysostosis multiplex stabilized. Had behavioral issues and required an aide for 1-on-1 schooling.

CaseBMT: N/A

Variant1: N/A

Variant1ClinVarID: N/A

Variant1CAID: N/A

Variant2: N/A

Variant2ClinVarID: N/A

Variant2CAID: N/A

AdditionalVariants: N/A

ParentalGenotype: N/A

PreviouslyPublished N/A

Case#: YS of sibship 9, female, 6.7 years old (age at diagnosis), 8.6 years old (age at ERT enrollment), 6.4 years (duration of ERT)

DiseaseAssertion: MPS1-HS

FamilyInfo: Affected OS (OS of sibship 9)

CasePresentingHPOs: HP:0007957, HP:0000943, HP:0002828 (Corneal opacity, dysostosis, joint contracture)

CaseHPOFreeText: Cardiac disease, ocular, respiratory, and musculoskeletal involvement.

CaseNotHPOs: N/A

CaseNotHPOFreeText: N/A

CaseEnzymeAssay: N/A

CaseUrineGAGs: N/A

CaseERT: Yes - Had stabilization of mild ocular symptoms, and cardiac disease remained less severe in the mild to moderate range. Had stabilization of dysostosis multiplex and no progression of motor function delays.

CaseBMT: N/A

Variant1: N/A

Variant1ClinVarID: N/A

Variant1CAID: N/A

Variant2: N/A

Variant2ClinVarID: N/A

Variant2CAID: N/A

AdditionalVariants: N/A

ParentalGenotype: N/A

PreviouslyPublished N/A

Case#: YS of Sibship 1, male, 0.2 years old (age at diagnosis), 0.3 years old (age at ERT enrollment), 4.5 years (duration of ERT)

DiseaseAssertion: MPS1-HS

FamilyInfo: Affected female OS (OS of sibship 1).

CasePresentingHPOs: Hernia (HP:0100790)

CaseHPOFreeText: N/A

CaseNotHPOs: HP:0007957, HP:0000943, HP:0002828 (Corneal opacity, dysostosis, joint contractures)

CaseNotHPOFreeText: Cardiac disease

CaseEnzymeAssay: N/A

CaseUrineGAGs: N/A

CaseERT: Yes - after almost 5 years of ERT, there was no development of cardiac or musculoskeletal disease.

CaseBMT: N/A

Variant1: c.1598C>G (p.P533R)

Variant1ClinVarID: 11910

Variant1CAID: CA256112

Variant2: c.1598C>G (p.P533R)

Variant2ClinVarID: 11910

Variant2CAID: CA256112

AdditionalVariants: N/A

ParentalGenotype: N/A

PreviouslyPublished N/A

Case#: YS1 of sibship 5 (see Table 1), male, 0.1 years old (age at diagnosis), 0.3 years old (age at ERT enrollment), 7.6 years (duration of ERT)

DiseaseAssertion: MPS1-HS

FamilyInfo: Two affected siblings (OS and YS2 of sibship 5)

CasePresentingHPOs: HP:0007957 (Corneal opacity)

CaseHPOFreeText: Cardiac disease

CaseNotHPOs: HP:0000943, HP:0002828 (Dysostosis, joint contractures)

CaseNotHPOFreeText: N/A

CaseEnzymeAssay: N/A

CaseUrineGAGs: N/A

CaseERT: Yes - Remained healthy, with the exception of mild ocular and cardiac symptoms. Psychomotor development remained normal and there were no limitations in ADL. Pulmonary function was between 70 and 94 % of normal at T2.

CaseBMT: N/A

Variant1: c.1469T>C (p.L490P)

Variant1ClinVarID: 11919

Variant1CAID: CA220503

Variant2: c.1469T>C (p.L490P)

Variant2ClinVarID: 11919

Variant2CAID: CA220503

AdditionalVariants: N/A

ParentalGenotype: N/A

PreviouslyPublished N/A

Case#: YS of sibship 6 (see Table 1), male, 0.6 years old (age at diagnosis), 3 years old (age at ERT enrollment), 7 years (duration of ERT)

DiseaseAssertion: MPS-HS

FamilyInfo: Two affected siblings (OS1 and OS2 of sibship 6)

CasePresentingHPOs: HP:0007957, HP:0000943, HP:0002828 (Corneal opacity, dysostosis, joint contractures)

CaseHPOFreeText: Cardiac disease, musculoskeletal symptoms

CaseNotHPOs: N/A

CaseNotHPOFreeText: N/A

CaseEnzymeAssay: N/A

CaseUrineGAGs: N/A

CaseERT: Yes - Pulmonary function was 70–80 % of normal and had no restrictions in ADL.

CaseBMT: N/A

Variant1: N/A

Variant1ClinVarID: N/A

Variant1CAID: N/A

Variant2: N/A

Variant2ClinVarID: N/A

Variant2CAID: N/A

AdditionalVariants: N/A

ParentalGenotype: N/A

PreviouslyPublished N/A

PMID: 26446585

Gene: IDUA

Disease: MPS1

Inheritance: Autosomal recessive

Case#: Patient 2 (see Table 2), 38 weeks, 1 day (Gestational age)

DiseaseAssertion: MPS1-H

FamilyInfo: N/A

CasePresentingHPOs: Inguinal hernia (HP:0000023)

CaseHPOFreeText: N/A

CaseNotHPOs: N/A

CaseNotHPOFreeText: Upper respiratory tract involvement

CaseEnzymeAssay: N/A

CaseUrineGAGs: N/A

CaseERT: N/A

CaseBMT: N/A

Variant1: c.1205G>A (p.W402X)

Variant1ClinVarID: 11908

Variant1CAID: CA220498

Variant2: c.208C>T (p.Q70X)

Variant2ClinVarID: 11909

Variant2CAID: CA204563

AdditionalVariants: N/A

ParentalGenotype: N/A

PreviouslyPublished N/A

Case#: Patient 7 (see Table 2), 33 weeks, 1 day (Gestational age)

DiseaseAssertion: MPS1-H

FamilyInfo: N/A

CasePresentingHPOs: N/A

CaseHPOFreeText: N/A

CaseNotHPOs: N/A

CaseNotHPOFreeText: N/A

CaseEnzymeAssay: 0.44 nmol x mg-1 × hr-1

CaseUrineGAGs: N/A

CaseERT: N/A

CaseBMT: N/A

Variant1: c.208C>T (p.Q70X)

Variant1ClinVarID: 11909

Variant1CAID: CA204563

Variant2: c.653T>C (p.L218P)

Variant2ClinVarID: 222995

Variant2CAID: CA356986

AdditionalVariants: N/A

ParentalGenotype: N/A

PreviouslyPublished N/A

Case#: Patient 29 (see Table 2), 40 weeks, 5 days (Gestational age)

DiseaseAssertion: MPS1-S

FamilyInfo: Sibling of Patient 28 (see Table 2)

CasePresentingHPOs: N/A

CaseHPOFreeText: N/A

CaseNotHPOs: Inguinal hernia (HP:0000023)

CaseNotHPOFreeText: Upper respiratory tract involvement

CaseEnzymeAssay: 1.61 nmol x mg-1 × hr-1

CaseUrineGAGs: N/A

CaseERT: N/A

CaseBMT: N/A

Variant1: c.474-2A>G (new nomenclature: c.386-2A>G)

Variant1ClinVarID: 222994

Variant1CAID: CA356991

Variant2: c.1148G>A (p.R383H)

Variant2ClinVarID: 558189

Variant2CAID: CA:2802205

AdditionalVariants: N/A

ParentalGenotype: N/A

PreviouslyPublished N/A

PMID: 23837464

Gene: IDUA

Disease: MPS1

Inheritance: Autosomal recessive

Case#: Patient 20 (see Table 2), 37 weeks, 1 day (Gestational age)

DiseaseAssertion: MPS1-H/S

FamilyInfo: Sibling of Patient 19 (see Table 2)

CasePresentingHPOs: N/A

CaseHPOFreeText: N/A

CaseNotHPOs: Inguinal hernia (HP:0000023)

CaseNotHPOFreeText: Upper respiratory tract involvement

CaseEnzymeAssay: 0.95 nmol x mg-1 × hr-1

CaseUrineGAGs: N/A

CaseERT: N/A

CaseBMT: N/A

Variant1: c.1205G>A (p.W402X)

Variant1ClinVarID: 11908

Variant1CAID: CA220498

Variant2: c.1044C>A (p.N348K)

Variant2ClinVarID: N/A

Variant2CAID: CA:355963142

AdditionalVariants: N/A

ParentalGenotype: N/A

PreviouslyPublished N/A

Case#: Patient 9 (see Table 2), 37 weeks, 2 days (Gestational age)

DiseaseAssertion: MPS1-H

FamilyInfo: N/A

CasePresentingHPOs: N/A

CaseHPOFreeText: Upper respiratory tract involvement

CaseNotHPOs: Inguinal hernia (HP:0000023)

CaseNotHPOFreeText: N/A

CaseEnzymeAssay: N/A

CaseUrineGAGs: N/A

CaseERT: N/A

CaseBMT: N/A

Variant1: c.208C>T (p.Q70X)

Variant1ClinVarID: 11909

Variant1CAID: CA204563

Variant2: c.653T>C (p.L218P)

Variant2ClinVarID: 222995

Variant2CAID: CA:356986

AdditionalVariants: N/A

ParentalGenotype: N/A

PreviouslyPublished N/A

Case#: Patient 21 (see Table 2), 41 weeks, 2 days (Gestational age)

DiseaseAssertion: MPS1-H/S

FamilyInfo: N/A

CasePresentingHPOs: N/A

CaseHPOFreeText: N/A

CaseNotHPOs: Inguinal hernia (HP:0000023)

CaseNotHPOFreeText: Upper respiratory tract involvement

CaseEnzymeAssay: 0.35 nmol x mg-1 × hr-1

CaseUrineGAGs: N/A

CaseERT: N/A

CaseBMT: N/A

Variant1: c.653T>C (p.L218P)

Variant1ClinVarID: 222995

Variant1CAID: CA356986

Variant2: c.943G>T (p.D315Y)

Variant2ClinVarID: N/A

Variant2CAID: CA:355962740

AdditionalVariants: N/A

ParentalGenotype: N/A

PreviouslyPublished N/A

Case#: Patient 18 (see Table 2), 40 weeks (Gestational age)

DiseaseAssertion: MPS1-H/S

FamilyInfo: N/A

CasePresentingHPOs: N/A

CaseHPOFreeText: Upper respiratory tract involvement

CaseNotHPOs: Inguinal hernia (HP:0000023)

CaseNotHPOFreeText: N/A

CaseEnzymeAssay: 0.77 nmol x mg-1 × hr-1

CaseUrineGAGs: N/A

CaseERT: N/A

CaseBMT: N/A

Variant1: c.1205G>A (p.W402X)

Variant1ClinVarID: 11908

Variant1CAID: CA220498

Variant2: c.1513C>G (p.R505G)

Variant2ClinVarID: 1482722

Variant2CAID: CA:355964784

AdditionalVariants: N/A

ParentalGenotype: N/A

PreviouslyPublished N/A

Case#: Patient 28 (see Table 2), 40 weeks, 5 days (Gestational age)

DiseaseAssertion: MPS1-S

FamilyInfo: Sibling of Patient 29 (see Table 2)

CasePresentingHPOs: N/A

CaseHPOFreeText: N/A

CaseNotHPOs: Inguinal hernia (HP:0000023)

CaseNotHPOFreeText: Upper respiratory tract involvement

CaseEnzymeAssay: N/A

CaseUrineGAGs: N/A

CaseERT: N/A

CaseBMT: N/A

Variant1: c.474-2A>G (new nomenclature:c.386-2A>G)

Variant1ClinVarID: 222994

Variant1CAID: CA356991

Variant2: c.1148G>A (p.R383H)

Variant2ClinVarID: 558189

Variant2CAID: CA:2802205

AdditionalVariants: N/A

ParentalGenotype: N/A

PreviouslyPublished N/A

Case#: Patient 13 (see Table 2), 38 weeks, 3 days (Gestational age)

DiseaseAssertion: MPS1-H

FamilyInfo: N/A

CasePresentingHPOs: N/A

CaseHPOFreeText: Upper respiratory tract involvement

CaseNotHPOs: Inguinal hernia (HP:0000023)

CaseNotHPOFreeText: N/A

CaseEnzymeAssay: 0.43 nmol x mg-1 × hr-1

CaseUrineGAGs: N/A

CaseERT: N/A

CaseBMT: N/A

Variant1: c.1205G>A (p.W402X)

Variant1ClinVarID: 11908

Variant1CAID: CA220498

Variant2: c.653T>C (p.L218P)

Variant2ClinVarID: 222995

Variant2CAID: CA:356986

AdditionalVariants: N/A

ParentalGenotype: N/A

PreviouslyPublished N/A

Case#: 18, Male, 15 years (onset), 15 years (diagnosed), 15 years (report)

DiseaseAssertion: Scheie Syndrome

FamilyInfo: Patients 17 and 18 are siblings

CasePresentingHPOs: HP:0004322, HP:0001387, HP:0002240, HP:0001744, HP:0001537, HP:0000280, HP:0000943 (Short Stature, Joint Stiffness, Hepatomegaly (moderate), Splenomegaly(mild), Umbilical Hernia, Coarse Facial Features (mild), Dysostosis Multiplex)

CaseHPOFreeText: (Mental Development (developmental quotient 93 at 15y, Verbal IQ 77; CIQ 79), Umbilical/Carpal Tunnel Syndrome)

CaseNotHPOs: HP:0000256 (Macrocephaly)

CaseNotHPOFreeText: N/A

CaseEnzymeAssay: N/A

CaseUrineGAGs: N/A

CaseERT: N/A

CaseBMT: N/A

GenotypingMethod: Not Provided

Variant1: p.Q380R

Variant1ClinVarID: 550799

Variant1CAID: CA2802202

Variant2: p.Q380R

Variant2ClinVarID: 550799

Variant2CAID: CA2802202

AdditionalVariants: p.A8/A8, p.A20/A20

ParentalGenotype: N/A

PreviouslyPublished N/A

Case#: 7, Female, 8 months (onset), 10 months (diagnosed), 5 years (report)

DiseaseAssertion: Hurler Syndrome

FamilyInfo: Not Provided

CasePresentingHPOs: HP:0000256, HP:0001387, HP:0002240, HP:0001537, HP:0000486, HP:0002857, HP:0012185, HP:0000280, HP:0000943, HP:0007957 (Macrocephaly (at 8m), Joint Stiffness (at 8m), Hepatomegaly (Severe before HSCT, mild after HSCT), Umbilical Hernia, Strabismus, genua valga, carpal tunnel syndrome, Coarse Facial Features (very mild), Dysostosis Multiplex, Corneal Clouding)

CaseHPOFreeText: Mental Development (developmental quotient 110 at 1y, Developmental quotient 115 at 5y), Normal psychomotor development, Hearing problems,

CaseNotHPOs: HP:0004322, HP:0001744 (Short Stature, Splenomegaly)

CaseNotHPOFreeText: N/A

CaseEnzymeAssay: normal IDUA activity in leucocytes (4 years after HSCT)

CaseUrineGAGs: N/A

CaseERT: N/A

CaseBMT: Hematopoietic Stem Cell Transplantation at 1y

GenotypingMethod: Not Provided

Variant1: p.W402X

Variant1ClinVarID: 11908

Variant1CAID: CA220498

Variant2: c.1650 + 5G > A

Variant2ClinVarID: 92634

Variant2CAID: CA220504

AdditionalVariants: N/A

ParentalGenotype: N/A

PreviouslyPublished N/A

Case#: 8, Male, 2, 5 years (onset), 3,5 months (diagnosed), 16 years (report)

DiseaseAssertion: Hurler-Scheie Syndrome

FamilyInfo: Not Provided

CasePresentingHPOs: HP:0000256, HP:0001387, HP:0002240, HP:0001744, HP:0001537, HP:001285, HP:0000280, HP:0000943, HP:0007957 (Macrocephaly, Joint Stiffness, Hepatomegaly (mild before HSCT), Splenomegaly (mild before HSCT), Umbilical Hernia, Carpal tunnel syndrome, Coarse Facial Features, Dysostosis Multiplex, Corneal Clouding)

CaseHPOFreeText: Mental Development (Borderline developmental quotient at 3y, IQ 117 at 12y)

CaseNotHPOs: HP:0004322, HP:0002240, HP:0001744 (Short Stature, Hepatomegaly (after HSCT), Splenomegaly (after HSCT))

CaseNotHPOFreeText: N/A

CaseEnzymeAssay: normal IDUA activity at 16 years

CaseUrineGAGs: N/A

CaseERT: N/A

CaseBMT: Hematopoietic Stem Cell Transplantation at 5y

GenotypingMethod: Not Provided

Variant1: p.W402X

Variant1ClinVarID: 11908

Variant1CAID: CA220498

Variant2: p.E640fs

Variant2ClinVarID: 558359

Variant2CAID: CA355966048

AdditionalVariants: N/A

ParentalGenotype: N/A

PreviouslyPublished N/A

Case#: 14, Male, 24 months (onset), 3 years (diagnosed), 8 years (report), deceased (at 9y)

DiseaseAssertion: Hurler Syndrome

FamilyInfo: Not Provided

CasePresentingHPOs: HP:0004322, HP:0000256, HP:0001387, HP:0002240, HP:0001744, HP:0001638, HP:0000023, HP:0002415, HP:0000158, HP:0000280, HP:0000943, HP:0007957 (Short Stature, Macrocephaly, Joint Stiffness, Hepatomegaly (severe), Splenomegaly (moderate), Cardiomyopathy (involvement of valves), Inguinal Hernia, Leukodystrophy (in MRI), Large Tongue, Coarse Facial Features, Dysostosis Multiplex, Corneal Clouding)

CaseHPOFreeText: (Mental Development (Delayed since infancy), Vision and Hearing impairment, Ear Inflammations, Cervical Canal Stenosis (in MRI at 7y), Tracheostomy)

CaseNotHPOs: N/A

CaseNotHPOFreeText: N/A

CaseEnzymeAssay: N/A

CaseUrineGAGs: N/A

CaseERT: N/A

CaseBMT: N/A

GenotypingMethod: Not Provided

Variant1: p.Q70X

Variant1ClinVarID: 11909

Variant1CAID: CA204563

Variant2: p.W626X

Variant2ClinVarID: 928997

Variant2CAID: CA355965968

AdditionalVariants: p.Q33H/Q33H, p.L118

ParentalGenotype: N/A

PreviouslyPublished N/A

PMID: 19396826

Gene: IDUA

Disease: MPS1

Inheritance: Autosomal recessive

Case#: 12, Female, 5 months (onset), 5 years (diagnosed), 5 years (report), deceased (at 7y)

DiseaseAssertion: Hurler Syndrome

FamilyInfo: Not Provided

CasePresentingHPOs: HP:0004322, HP:0000256, HP:0001387, HP:0002240, HP:0001744, HP:0001537, HP:0000365, HP:0000280, HP:0000943, HP:0007957 (Short Stature, Macrocephaly, Joint Stiffness, Hepatomegaly (Severe), Splenomegaly (moderate), Umbilical Hernia, Deafness (progressive), Coarse Facial Features, Dysostosis Multiplex, Corneal Clouding)

CaseHPOFreeText: Mental Development (Delayed)

CaseNotHPOs: N/A

CaseNotHPOFreeText: N/A

CaseEnzymeAssay: N/A

CaseUrineGAGs: N/A

CaseERT: N/A

CaseBMT: N/A

GenotypingMethod: Not Provided

Variant1: p.Q70X

Variant1ClinVarID: 11909

Variant1CAID: CA204563

Variant2: p.D315Y

Variant2ClinVarID: N/A

Variant2CAID: CA355962740

AdditionalVariants: p.A8, p.A20, p.Q33H, p.L118

ParentalGenotype: N/A

PreviouslyPublished N/A

Case#: 9, Female, 3-4 years (onset), 4 years (diagnosed), 20 years (report), deceased (accidentally at 21y)

DiseaseAssertion: Hurler-Scheie Syndrome

FamilyInfo: Not Provided

CasePresentingHPOs: HP:0000256, HP:0001387, HP:0002240, HP:0001744, HP:0001639, HP:001285, HP:0000158, HP:0000280, HP:0000943, HP:0007957 (Macrocephaly, Joint Stiffness (Severe and progressive), Hepatomegaly (Severe at diagnosis but none at report), Splenomegaly (mild at diagnosis and report), Hypertrophic Cardiomyopathy (Progressive), Carpal tunnel syndrome, Large Tongue, Coarse Facial Features, Dysostosis Multiplex, Corneal Clouding)

CaseHPOFreeText: Mental Development (Uneven Development at 2y; IQ 117 at 12y)

CaseNotHPOs: HP:0004322 (Short Stature)

CaseNotHPOFreeText: N/A

CaseEnzymeAssay: N/A

CaseUrineGAGs: N/A

CaseERT: ERT since 18y

CaseBMT: N/A

GenotypingMethod: Not Provided

Variant1: p.W402X

Variant1ClinVarID: 11908

Variant1CAID: CA220498

Variant2: p.E640fs

Variant2ClinVarID: 558359

Variant2CAID: CA355966048

AdditionalVariants: N/A

ParentalGenotype: N/A

PreviouslyPublished N/A

Case#: 20, Female, infancy (onset), 2 years (diagnosed), 2 years (report)

DiseaseAssertion: Hurler Syndrome

FamilyInfo: N/A

CasePresentingHPOs: HP:0004322, HP:0002240, HP:0001744, HP:0000280, HP:0000943, HP:0007957 (Short Stature, Hepatomegaly, Splenomegaly, Coarse Facial Features, Dysostosis Multiplex, Corneal Clouding)

CaseHPOFreeText: (Mental Development (delayed since early infancy), Mild LV hypertrophy, Frequent respiratory infections, Vision Impairment and Hearing Loss)

CaseNotHPOs: N/A

CaseNotHPOFreeText: N/A

CaseEnzymeAssay: N/A

CaseUrineGAGs: N/A

CaseERT: N/A

CaseBMT: N/A

GenotypingMethod: Not Provided

Variant1: p.V620F

Variant1ClinVarID: 1067173

Variant1CAID: CA355965934

Variant2: p.V620F

Variant2ClinVarID: 1067173

Variant2CAID: CA355965934

AdditionalVariants: p.R105Q/R105Q, p.N181/N181, p.A314/A314, p.A361T/A361T, p.T388/T388, p.T410/T410, p.V454I/V454I, p.R489/R489

ParentalGenotype: N/A

PreviouslyPublished N/A

Case#: Patient 8 (see Table 2), male, 22.3 years old (age at report), 12.5 years (duration of treatment), 8 surgeries

DiseaseAssertion: MPS1-HS

FamilyInfo: N/A

CasePresentingHPOs: N/A

CaseHPOFreeText: N/A

CaseNotHPOs: HP:0000238, HP:0002176, HP:0002360 (Hydrocephalus, spinal cord compression, sleep abnormality)

CaseNotHPOFreeText: Shunt placement, psychiatric problems

CaseEnzymeAssay: N/A

CaseUrineGAGs: N/A

CaseERT: Yes

CaseBMT: N/A

Variant1: c.793G>C (p.G265R)

Variant1ClinVarID: 638074

Variant1CAID: CA2802098

Variant2: c.979G>C (p.A327P)

Variant2ClinVarID: 167190

Variant2CAID: CA234128

AdditionalVariants: N/A

ParentalGenotype: N/A

PreviouslyPublished N/A

Case#: Patient 2 (see Table 2), male, 18.3 years old (age at report), 9.1 years (duration of treatment), 7 surgeries

DiseaseAssertion: MPS1-HS

FamilyInfo: N/A

CasePresentingHPOs: HP:0000238, HP:0002176, HP:0002360 (Hydrocephalus, spinal cord compression, sleep abnormality)

CaseHPOFreeText: Shunt placement, psychiatric problems

CaseNotHPOs: N/A

CaseNotHPOFreeText: N/A

CaseEnzymeAssay: N/A

CaseUrineGAGs: N/A

CaseERT: Yes

CaseBMT: N/A

Variant1: c.712T>A (p.L238Q) CDNA and protein change do not match. Known variant p.L238Q has a CDNA change of c.713T>A.

Variant1ClinVarID: 265418

Variant1CAID: CA2802065

Variant2: c.1205G>A (p.W402X)

Variant2ClinVarID: 11908

Variant2CAID: CA220498

AdditionalVariants: N/A

ParentalGenotype: N/A

PreviouslyPublished N/A

Case#: Patient 4 (see Table 2), female, 19.8 years old (age at report), 9.7 years (duration of treatment), 8 surgeries

DiseaseAssertion: MPS1-HS

FamilyInfo: N/A

CasePresentingHPOs: HP:0000238, HP:0002360 (Hydrocephalus, sleep abnormality)

CaseHPOFreeText: Shunt placement, psychiatric problems

CaseNotHPOs: HP:0002176 (Spinal cord compression)

CaseNotHPOFreeText: N/A

CaseEnzymeAssay: N/A

CaseUrineGAGs: N/A

CaseERT: Yes

CaseBMT: N/A

Variant1: c.712T>A (p.L238Q) CDNA and protein change do not match. Known variant p.L238Q has a CDNA change of c.713T>A.

Variant1ClinVarID: 265418

Variant1CAID: CA2802065

Variant2: c.1205G>A (p.W402X)

Variant2ClinVarID: 11908

Variant2CAID: CA220498

AdditionalVariants: N/A

ParentalGenotype: N/A

PreviouslyPublished N/A

Case#: Patient 7 (see Table 2), male, 15.1 years old (age at report), 6.9 years (duration of treatment), 6 surgeries

DiseaseAssertion: MPS1-HS

FamilyInfo: N/A

CasePresentingHPOs: N/A

CaseHPOFreeText: N/A

CaseNotHPOs: HP:0000238, HP:0002176, HP:0002360 (Hydrocephalus, spinal cord compression, sleep abnormality)

CaseNotHPOFreeText: Shunt placement, psychiatric problems

CaseEnzymeAssay: N/A

CaseUrineGAGs: N/A

CaseERT: Yes

CaseBMT: N/A

Variant1: (p.G256R) Potential type error, p.G256R does not exist, possible should be p.G265R as seen in Patient 8.

Variant1ClinVarID: N/A

Variant1CAID: N/A

Variant2: c.1205G>A (p.W402X)

Variant2ClinVarID: 11908

Variant2CAID: CA220498

AdditionalVariants: N/A

ParentalGenotype: N/A

PreviouslyPublished N/A

Case#: Patient 12 (see Table 2), female, 20.9 years old (age at report), 9.3 years (duration of treatment), 10 surgeries

DiseaseAssertion: MPS1-HS

FamilyInfo: N/A

CasePresentingHPOs: HP:0002176 (Spinal cord compression)

CaseHPOFreeText: N/A

CaseNotHPOs: HP:0000238, HP:0002360 (Hydrocephalus, sleep abnormality)

CaseNotHPOFreeText: Shunt placement

CaseEnzymeAssay: N/A

CaseUrineGAGs: N/A

CaseERT: Yes

CaseBMT: N/A

Variant1: c.1205G>A (p.W402X)

Variant1ClinVarID: 11908

Variant1CAID: CA220498

Variant2: (Int11-7c>t) Current HGVS nomenclature is c.1651-7C>T

Variant2ClinVarID: 1147380

Variant2CAID: CA438057995

AdditionalVariants: N/A

ParentalGenotype: N/A

PreviouslyPublished N/A

Case#: Patient 5, Male, 1 year 4 months (diagnosed), 4 years (report), Djerba Island (Tunisian origin)

DiseaseAssertion: N/A

FamilyInfo: Parents are consanguineous between 3rd cousins

CasePresentingHPOs: N/A

CaseHPOFreeText: N/A

CaseNotHPOs: N/A

CaseNotHPOFreeText: N/A

CaseEnzymeAssay: Leukocyte IDUA activity 0.2% (% normal) ; determined in sonicated leukocyte pellets using the artificial substrate 4-methylumbellifery IDUA

CaseUrineGAGs: N/A

CaseERT: N/A

CaseBMT: N/A

GenotypingMethod: Sequencing exons and intro-exon junctions; Phenol/chloroform procedure

Variant1: p.P533R

Variant1ClinVarID: 11910

Variant1CAID: CA256112

Variant2: p.P533R

Variant2ClinVarID: 11910

Variant2CAID: CA256112

AdditionalVariants: N/A

ParentalGenotype: N/A

PreviouslyPublished N/A

PMID: 31236806

Gene: IDUA

Disease: MPS1

Inheritance: Autosomal recessive

Case#: Patient #2 (see Table 2), male, 2 years old (age at diagnosis), 12 years old (age at report)

DiseaseAssertion: MPS-I

FamilyInfo: Born from a consanguineous marriage

CasePresentingHPOs: Cardiomyopathy, scoliosis, macroglossia, failure to thrive, global developmental delay, short stature, skeletal dysplasia, hepatomegaly, splenomegaly (HP:0001638, HP:0002650, HP:0000158, HP:0001508, HP:0001263, HP:0004322, HP:0002652, HP:0002240, HP:0001744)

CaseHPOFreeText: Normal intelligence, mitral valve thickening

CaseNotHPOs: N/A

CaseNotHPOFreeText: N/A

CaseEnzymeAssay: α-L-iduronidase 0.5 nmol/ml. The activity of this enzyme is below its reference (1–18.5 nmol/ml).

CaseUrineGAGs: N/A

CaseERT: N/A

CaseBMT: N/A

Variant1: c.903C>G (p.D301E)

Variant1ClinVarID: 1458511

Variant1CAID: CA355962528

Variant2: c.903C>G (p.D301E)

Variant2ClinVarID: 1458511

Variant2CAID: CA355962528

AdditionalVariants: N/A

ParentalGenotype: N/A

PreviouslyPublished N/A

Case#: Patient #1 (see Table 2), male, 6 months old (age at diagnosis), 7 years old (age at report)

DiseaseAssertion: MPS I

FamilyInfo: Born from a consanguineous marriage

CasePresentingHPOs: Scoliosis, developmental delay, short stature, macrocephaly, coarse facial features, hepatomegaly (HP:0002650, HP:0001263, HP:0004322, HP:0000256, HP:0000256, HP:0002240)

CaseHPOFreeText: Irregular chest, respiratory problems

CaseNotHPOs: N/A

CaseNotHPOFreeText: N/A

CaseEnzymeAssay: α-L-iduronidase 1.18 nmol/spot. The activity of this enzyme is below its reference (450–2600 nmol/spot).

CaseUrineGAGs: N/A

CaseERT: N/A

CaseBMT: N/A

Variant1: c.469T>C (p.S157P)

Variant1ClinVarID: N/A

Variant1CAID: CA355961573

Variant2: c.469T>C (p.S157P)

Variant2ClinVarID: N/A

Variant2CAID: CA355961573

AdditionalVariants: N/A

ParentalGenotype: N/A

PreviouslyPublished N/A

PMID: 34573925

Gene: IDUA

Disease: MPS1

Inheritance: Autosomal recessive

Case#: Patient F, female, 25 years old (age at report), 61 kg of weight (50th percentile), height of 154 cm (10th percentile). She is now working as an office secretary and also practices aerobic activity three times a week. She drives a car autonomously with her driving license which is renewed every 2 years. Her quality of life was measured with EQ-5D-Y and resulted good (100/100). Overall cognitive abilities are in the lower average expected for age (IQ:80), with difficulties in executive functioning, working memory, and arithmetic reasoning.

DiseaseAssertion: attenuated form of MPS-1

FamilyInfo: Affected younger sibling (Patient M), born to non-consanguineous Italian parents.

CasePresentingHPOs: Moderate facial coarseness, moderately severe dysostosis multiplex, scoliosis, hyperlordosis, genua valga, corneal clouding, hyperopia, astigmatism, otitis media (completely corrected by eyeglasses), hearing impairment, mild obstructive sleep apnea (since 16 years old), mild thickened skin (HP:0000280, HP:0000943, HP:0002650, HP:0003307, HP:0002857, HP:0007957, HP:0000540, HP:0000483, HP:0000388, HP:0000365, HP:0010535, HP:0001072)

CaseHPOFreeText: Liver and spleen volumes were normalized within the first year of ERT and remained within normal limits at clinical examination, claw feet, stiffness of the tibio-tarsal joint, ROM of hip and knees were within the normal ranges, improved stiffness of the trunk, movements of shoulders, elbows and wrists were within the normal range, limited flexion of fingers due to mild rigidity, normal cerebral MRI, a mild–moderate tricuspid insufficiency with pulmonary artery pressure (PAP) within the upper normal range (25 mmHG) was reported (at 16 years old), cardiac involvement.

CaseNotHPOs: N/A

CaseNotHPOFreeText: N/A

CaseEnzymeAssay: N/A

CaseUrineGAGs: Total urinary GAG excretion was slightly above the upper limit of the normal range (47 μg/mg creatinine with normal values < 26) with the qualitative assay showing a band of DS.

CaseERT: Yes - Began ERT and 5 years old. Laronidase infusions were started delivering weekly (at the dose of 0.5 mg/kg) using implanted venous access devices. Laronidase infusion generally lasted approximately 4 h, without the need for any premedication.

CaseBMT: N/A

Variant1: c.1205G>A (p.W402X)

Variant1ClinVarID: 11908

Variant1CAID: CA220498

Variant2: c.1603C>T (p.L535F)

Variant2ClinVarID: 638076

Variant2CAID: CA355865038

AdditionalVariants: N/A

ParentalGenotype: N/A

PreviouslyPublished Yes (PMID: 20026495) and (PMID:26965916)

Case#: Patient M, male, 19 years of age (age at report), 71 kg of weight (50th percentile), height of 171 cm (25th percentile). He attended the last year of high school Institute of Art and practices aerobic activity three times a week. He is intellectually normal (IQ: 108) with a good quality of life (100/100 assessed by EQ-5D-Y).

DiseaseAssertion: attenuated form of MPS 1

FamilyInfo: Affected older sibling (Patient F), born to non-consanguineous Italian parents.

CasePresentingHPOs: Mild facial coarseness, temporomandibular joint dislocation, hypoplasia of the odontoid process, severe worsening of corneal clouding (noted at 12 months), mild hyperopia (noted at 7 years), astigmatism (noted at 7 years but completely corrected by eyeglasses), minimal multiplex dysostosis, mild joint stiffness, kyphosis, initial signs of carpal tunnel syndrome (HP:0000280, HP:6000814, HP:0003311, HP:0007957, HP:0000540, HP:0000483, HP:0000943, HP:0001387, HP:0002808, HP:0012185)

CaseHPOFreeText: Mild shoulder stiffness was present with limited forward elevation up to 120° and in abduction up to 100°, mild scoliosis with Cobb angle of 17°, triangular shape of cervical and thoracic vertebres (C4, C5, C6, D6, and D7), several dorsal herniated discs, normal brain MRI, mild heart involvement, stabilization of the cardiac valvulopathy, normal hearing.

CaseNotHPOs: Hepatosplenomegaly (HP:0001433)

CaseNotHPOFreeText: Respiratory or sleep disturbances, no recurrent infections.

CaseEnzymeAssay: N/A

CaseUrineGAGs: Total urinary glycosaminoglycans (GAG) determination on samples collected just before infusion remained within normal ranges (20,8 μg/mg creatinine with normal values < 42) but at the qualitative assay was present a band of DS.

CaseERT: Yes - Began ERT at 5 months old (pre symptomatically). Laronidase infusions were started delivering weekly (at the dose of 0.5 mg/kg) using implanted venous access devices. Laronidase infusion generally lasted approximately 4 h, without the need for any premedication.

CaseBMT: N/A

Variant1: c.1205G>A (p.W402X)

Variant1ClinVarID: 11908

Variant1CAID: CA220498

Variant2: c.1603C>T (p.L535F)

Variant2ClinVarID: 638076

Variant2CAID: CA355865038

AdditionalVariants: N/A

ParentalGenotype: N/A

PreviouslyPublished Yes (PMID: 20026495) and (PMID:26965916)

PMID: 36333985

Gene: IDUA

Disease: MPS1

Inheritance: Autosomal recessive

Case#: Patient 9, 4 years old, Iranian

DiseaseAssertion: MPS1-S (Attenuated)

FamilyInfo: N/A

CasePresentingHPOs: N/A

CaseHPOFreeText: N/A

CaseNotHPOs: N/A

CaseNotHPOFreeText: N/A

CaseEnzymeAssay: 0.19 µmol/g.h (Normal ranges: 10-50 µmol/g.h)

CaseUrineGAGs: N/A

CaseERT: N/A

CaseBMT: N/A

Variant1: c.903C>G (p.D301E)

Variant1ClinVarID: 1458511

Variant1CAID: CA355962528

Variant2: c.903C>G (p.D301E)

Variant2ClinVarID: 1458511

Variant2CAID: CA355962528

AdditionalVariants: N/A

ParentalGenotype: N/A

PreviouslyPublished N/A

Case#: Patient 2, 12 years old, Iranian

DiseaseAssertion: MPS1-S (Attenuated)

FamilyInfo: N/A

CasePresentingHPOs: N/A

CaseHPOFreeText: N/A

CaseNotHPOs: N/A

CaseNotHPOFreeText: N/A

CaseEnzymeAssay: 0.3 µmol/g.h (Normal ranges: 10-50 µmol/g.h)

CaseUrineGAGs: N/A

CaseERT: N/A

CaseBMT: N/A

Variant1: c.401G>T (p.G134V)

Variant1ClinVarID: N/A

Variant1CAID: CA355961317

Variant2: c.401G>T (p.G134V)

Variant2ClinVarID: N/A

Variant2CAID: CA355961317

AdditionalVariants: N/A

ParentalGenotype: N/A

PreviouslyPublished N/A

Case#:Patient Sample unique ID 5, Infant screened positive at birth (specimens with activity ≤15% of the DMA for enzyme activity and a CLIR screening algorithm result of indeterminate or MPS I)

DiseaseAssertion:Carrier

FamilyInfo:None

CasePresentingHPOs:None

CaseHPOFreeText:None

CaseNotHPOs:None

CaseNotHPOFreeText: Normal examination at follow up after screening positive at birth (specimens with activity ≤15% of the DMA for enzyme activity and a CLIR screening algorithm result of indeterminate or MPS I)

CaseEnzymeAssay: IDUA activity 0.198 (9.2) umol/L/h (%DMA) during new born screening through dried blood spot (plasma) and 9.2 pmol/punch/h Confirmatory IDUA enzyme measured at follow-up appointment

CaseUrineGAGs: DS 4.6 g/mol creatinine and HS 6.1 g/mol creatinine (Normal)

CaseERT:No

CaseBMT:No

Variant1:heterozygous pathogenic: c.1029C>G; p.Y343* (Normal examination)

Variant1ClinVarID: 560781

Variant1CAID: CA352049896

Variant2: heterozygous PD: c.235G>A; p.A79T (Carrier)

Variant2ClinVarID:41682

Variant2CAID:CA000358

AdditionalVariants:heterozygous PD: c.296C>T; p.T99I (ClinVarID:53610, CAID:CA326991)

ParentalGenotype:N/A

PreviouslyPublished:N/A

Case#:Patient Sample unique ID 31, Infant screened positive at birth (specimens with activity ≤15% of the DMA for enzyme activity and a CLIR screening algorithm result of indeterminate or MPS I)

DiseaseAssertion:None

FamilyInfo:None

CasePresentingHPOs:None

CaseHPOFreeText:None

CaseNotHPOs:None

CaseNotHPOFreeText: Normal examination at follow up after screening positive at birth (specimens with activity ≤15% of the DMA for enzyme activity and a CLIR screening algorithm result of indeterminate or MPS I)

CaseEnzymeAssay: IDUA activity 0.423 (7.9) umol/L/h (%DMA) during new born screening through dried blood spot (plasma) and 7.9 pmol/punch/h Confirmatory IDUA enzyme

CaseUrineGAGs: DS 2.7 g/mol creatinine and HS 2.5 g/mol creatinine (Normal)

CaseERT:No

CaseBMT:No

Variant1:homozygous PD: c.235G>A; p.A79T (Normal examination)

Variant1ClinVarID:41682

Variant1CAID: CA000358

Variant2: homozygous PD: c.296C>T; p.T99I

Variant2ClinVarID:53610

Variant2CAID:CA326991

AdditionalVariants:None

ParentalGenotype:None provided

PreviouslyPublished:N/A

Case#:Patient Sample unique ID 58, Infant screened positive at birth (specimens with activity ≤15% of the DMA for enzyme activity and a CLIR screening algorithm result of indeterminate or MPS I)

DiseaseAssertion:None

FamilyInfo:None

CasePresentingHPOs:None

CaseHPOFreeText:None

CaseNotHPOs:None

CaseNotHPOFreeText: Normal examination at follow up after screening positive at birth (specimens with activity ≤15% of the DMA for enzyme activity and a CLIR screening algorithm result of indeterminate or MPS I)

CaseEnzymeAssay: IDUA activity 0.413 (8.7) umol/L/h (%DMA) during new born screening through dried blood spot (plasma) and 8.7 pmol/punch/h Confirmatory IDUA enzyme

CaseUrineGAGs: N/A (Family refused to collect additional urine specimen.)

CaseERT:No

CaseBMT:No

Variant1:homozygous PD: c.235G>A; p.A79T (Normal examination)

Variant1ClinVarID:41682

Variant1CAID: CA000358

Variant2: homozygous PD: c.296C>T; p.T99I

Variant2ClinVarID:53610

Variant2CAID:CA326991

AdditionalVariants: heterozygous PD: c.667G>A; p.D223N (ClinVarID: 2220838, CAID: CA363422841)

ParentalGenotype:None provided

PreviouslyPublished:N/A

Case#: Patient 2

DiseaseAssertion: MPS1-H

FamilyInfo: N/A

CasePresentingHPOs: N/A

CaseHPOFreeText: N/A

CaseNotHPOs: N/A

CaseNotHPOFreeText: N/A

CaseEnzymeAssay: N/A

CaseUrineGAGs: N/A

CaseERT: N/A

CaseBMT: N/A

Variant1: c.208C>T (p.Q70X)

Variant1ClinVarID: 11909

Variant1CAID: CA204563

Variant2: c.398_403del (p.Met133_Gly134del)

Variant2ClinVarID: 863830

Variant2CAID: CA2801912

AdditionalVariants: N/A

ParentalGenotype: N/A

PreviouslyPublished N/A

Case#: Patient 5, male, 7.5 months (age at HSCT), 5.3 months (age at ERT).

DiseaseAssertion: MPS1-H

FamilyInfo: N/A

CasePresentingHPOs: Pneumonia (HP:0002090)

CaseHPOFreeText: Adenovirus, gastrointestinal and skin (GVHD)

CaseNotHPOs: N/A

CaseNotHPOFreeText: N/A

CaseEnzymeAssay: 0.2 (at diagnosis), 38.3 (after HSCT) Units not provided.

CaseUrineGAGs: N/A

CaseERT: Yes - 87 days duration

CaseBMT: Yes - MUD (matched unrelated donor) with stem cells sourcing from the CB (cord blood)

Variant1: c.208C>T (p.Q70X)

Variant1ClinVarID: 11909

Variant1CAID: CA204563

Variant2: c.1205G>A (p.W402X)

Variant2ClinVarID: 11908

Variant2CAID: CA220498

AdditionalVariants: N/A

ParentalGenotype: N/A

PreviouslyPublished N/A

Case#: Patient 1, male, 6.9 months (age at HSCT), 4.2 months (age at ERT)

DiseaseAssertion: MPS1-H

FamilyInfo: N/A

CasePresentingHPOs: Autoimmune hemolysis (HP:0001890)

CaseHPOFreeText: Rhinovirus pneumonitis

CaseNotHPOs: N/A

CaseNotHPOFreeText: N/A

CaseEnzymeAssay: 0.22 (at diagnosis), 55.5 (post HSCT) Units not provided.

CaseUrineGAGs: N/A

CaseERT: Yes - 83 days duration

CaseBMT: Yes - MUD (matched unrelated donor) with stem cells sourcing from the CB (cord blood)

Variant1: c.1205G>A (p.W402X)

Variant1ClinVarID: 11908

Variant1CAID: CA220498

Variant2: c.1205G>A (p.W402X)

Variant2ClinVarID: 11908

Variant2CAID: CA220498

AdditionalVariants: N/A

ParentalGenotype: N/A

PreviouslyPublished N/A

Case#: Patient 2: Enrolled in study at 9.9 years, female, onset at 0.3 years, diagnosed at 5.2 years, ERT started 7.9 years DiseaseAssertion:MPS1 H FamilyInfo:No consanguinity, Sister similarly affected CasePresentingHPOs:Corneal opacity (HP:0007957), Joint stiffness (HP:0001387), Macrocephaly (HP:0000256), CaseHPOFreeText: CaseNotHPOs: Hepatosplenomegaly (HP:0001433) CaseNotHPOFreeText: CaseEnzymeAssay: CaseUrineGAGs: 0.36(min)-4.55(max) mg GAG/mmol creatinine while on ERT CaseERT: Laronidase dose-optimization trial : standard regimen – 0.58 mg/kg/week; biweekly regimen – 1.2 mg/kg every two weeks CaseBMT:Nil Variant1:P533R Variant1ClinVarID:11910 Variant1CAID:CA256112 Variant2:P533R Variant2ClinVarID:11910 Variant2CAID:CA256112 AdditionalVariants:Nil ParentalGenotype:NA PreviouslyPublishedNA

Case#: Variant not associated with a proband. Variant listed in supplementary materials in Supplementary Table 4

DiseaseAssertion: Mucopolysaccharidosis type I, MPS I

FamilyInfo: N/A

CasePresentingHPOs:

CaseHPOFreeText:

CaseNotHPOs:

CaseNotHPOFreeText:

CaseEnzymeAssay: N/A

CaseUrineGAGs: N/A

CaseERT: N/A

CaseBMT: N/A

Variant1: L218P

Variant1ClinVarID: 222995

Variant1CAID:CA356986

Variant2: N/A

Variant2ClinVarID: N/A

Variant2CAID: N/A

AdditionalVariants: N/A

ParentalGenotype: N/A

PreviouslyPublished: N/A

Case#: Variant not associated with a proband. Variant listed in supplementary materials in Supplementary Table 4

DiseaseAssertion: Mucopolysaccharidosis type I, MPS I

FamilyInfo: N/A

CasePresentingHPOs:

CaseHPOFreeText:

CaseNotHPOs:

CaseNotHPOFreeText:

CaseEnzymeAssay: N/A

CaseUrineGAGs: N/A

CaseERT: N/A

CaseBMT: N/A

Variant1: L535F

Variant1ClinVarID: 638076

Variant1CAID: CA355965038

Variant2: N/A

Variant2ClinVarID: N/A

Variant2CAID: N/A

AdditionalVariants: N/A

ParentalGenotype: N/A

PreviouslyPublished: N/A

Case#: Variant not associated with a proband. Variant listed in supplementary materials in Supplementary Table 4

DiseaseAssertion: Mucopolysaccharidosis type I, MPS I

FamilyInfo: N/A

CasePresentingHPOs:

CaseHPOFreeText:

CaseNotHPOs:

CaseNotHPOFreeText:

CaseEnzymeAssay: N/A

CaseUrineGAGs: N/A

CaseERT: N/A

CaseBMT: N/A

Variant1: N348K

Variant1ClinVarID:

Variant1CAID: CA355963142

Variant2: N/A

Variant2ClinVarID: N/A

Variant2CAID: N/A

AdditionalVariants: N/A

ParentalGenotype: N/A

PreviouslyPublished: N/A

Case#: Variant not associated with a proband. Variant listed in supplementary materials in Supplementary Table 4

DiseaseAssertion: Mucopolysaccharidosis type I, MPS I

FamilyInfo: N/A

CasePresentingHPOs:

CaseHPOFreeText:

CaseNotHPOs:

CaseNotHPOFreeText:

CaseEnzymeAssay: N/A

CaseUrineGAGs: N/A

CaseERT: N/A

CaseBMT: N/A

Variant1: L238Q

Variant1ClinVarID: 265418

Variant1CAID: CA2802065

Variant2: N/A

Variant2ClinVarID: N/A

Variant2CAID: N/A

AdditionalVariants: N/A

ParentalGenotype: N/A

PreviouslyPublished: N/A

Case#: Variant not associated with a proband. Variant listed in supplementary materials in Supplementary Table 4

DiseaseAssertion: Mucopolysaccharidosis type I, MPS I

FamilyInfo: N/A

CasePresentingHPOs:

CaseHPOFreeText:

CaseNotHPOs:

CaseNotHPOFreeText:

CaseEnzymeAssay: N/A

CaseUrineGAGs: N/A

CaseERT: N/A

CaseBMT: N/A

Variant1: V279A

Variant1ClinVarID:

Variant1CAID: CA355962380

Variant2: N/A

Variant2ClinVarID: N/A

Variant2CAID: N/A

AdditionalVariants: N/A

ParentalGenotype: N/A

PreviouslyPublished: N/A

Case#: Variant not associated with a proband. Variant listed in supplementary materials in Supplementary Table 4

DiseaseAssertion: Mucopolysaccharidosis type I, MPS I

FamilyInfo: N/A

CasePresentingHPOs:

CaseHPOFreeText:

CaseNotHPOs:

CaseNotHPOFreeText:

CaseEnzymeAssay: N/A

CaseUrineGAGs: N/A

CaseERT: N/A

CaseBMT: N/A

Variant1: T103P

Variant1ClinVarID:

Variant1CAID: CA355960996

Variant2: N/A

Variant2ClinVarID: N/A

Variant2CAID: N/A

AdditionalVariants: N/A

ParentalGenotype: N/A

PreviouslyPublished: N/A

Case#: Variant not associated with a proband. Variant listed in supplementary materials in Supplementary Table 4

DiseaseAssertion: Mucopolysaccharidosis type I, MPS I

FamilyInfo: N/A

CasePresentingHPOs:

CaseHPOFreeText:

CaseNotHPOs:

CaseNotHPOFreeText:

CaseEnzymeAssay: N/A

CaseUrineGAGs: N/A

CaseERT: N/A

CaseBMT: N/A

Variant1: G409R

Variant1ClinVarID: 1084956

Variant1CAID: CA91169920

Variant2: N/A

Variant2ClinVarID: N/A

Variant2CAID: N/A

AdditionalVariants: N/A

ParentalGenotype: N/A

PreviouslyPublished: N/A

Case#: Variant not associated with a proband. Variant listed in supplementary materials in Supplementary Table 4

DiseaseAssertion: Mucopolysaccharidosis type I, MPS I

FamilyInfo: N/A

CasePresentingHPOs:

CaseHPOFreeText:

CaseNotHPOs:

CaseNotHPOFreeText:

CaseEnzymeAssay: N/A

CaseUrineGAGs: N/A

CaseERT: N/A

CaseBMT: N/A

Variant1: S633L

Variant1ClinVarID: 556406

Variant1CAID: CA355966010

Variant2: N/A

Variant2ClinVarID: N/A

Variant2CAID: N/A

AdditionalVariants: N/A

ParentalGenotype: N/A

PreviouslyPublished: N/A

Case#: Patient 19, born in 2004 (paper published in 2017), 11 months (age at first treatment)

DiseaseAssertion: MPSI-H

FamilyInfo: N/A

CasePresentingHPOs: Corneal clouding (HP:0007957)

CaseHPOFreeText: N/A

CaseNotHPOs: Retinopathy, cataract (HP:0000488, HP:0000518)

CaseNotHPOFreeText: N/A

CaseEnzymeAssay: 66 ng/mol (56 weight matched enzyme reference assay)

CaseUrineGAGs: 0.55 DS/CS

CaseERT: Yes

CaseBMT: Yes, Cord

Variant1: c.1205G>A (p.W402X)

Variant1ClinVarID: 11908

Variant1CAID: CA220498

Variant2: c.1205G>A (p.W402X)

Variant2ClinVarID: 11908

Variant2CAID: CA220498

AdditionalVariants: N/A

ParentalGenotype: N/A

PreviouslyPublished N/A

Case#: Patient 1, born in 2007 (paper published in 2017), 9 months (age at first treatment)

DiseaseAssertion: MPSI-H

FamilyInfo: N/A

CasePresentingHPOs: Corneal clouding (HP:0007957)

CaseHPOFreeText: N/A

CaseNotHPOs: Retinopathy, cataract (HP:0000488, HP:0000518)

CaseNotHPOFreeText: N/A

CaseEnzymeAssay: 44.29 ng/mol (33.09 weight matched enzyme reference assay)

CaseUrineGAGs: 0.4 DS/CS

CaseERT: Yes

CaseBMT: Yes, cord

Variant1: c.208C>T (p.Q70X)

Variant1ClinVarID: 11909

Variant1CAID: CA204563

Variant2: c.979G>C (p.A327P)

Variant2ClinVarID: 167190

Variant2CAID: CA234128

AdditionalVariants: N/A

ParentalGenotype: N/A

PreviouslyPublished N/A

Case#: Patient 5, born in 1991 (paper published in 2017), 10 months (age at first treatment)

DiseaseAssertion: MPSI-H

FamilyInfo: N/A

CasePresentingHPOs: Corneal clouding, retinopathy (HP:0007957, HP:0000488)

CaseHPOFreeText: N/A

CaseNotHPOs: Cataract (HP:0000518)

CaseNotHPOFreeText: N/A

CaseEnzymeAssay: 21.6 ng/mol (40.9 weight matched enzyme reference assay)

CaseUrineGAGs: 0.79 DS/CS

CaseERT: No

CaseBMT: Yes, Sib

Variant1: c.1205G>A (p.W402X)

Variant1ClinVarID: 11908

Variant1CAID: CA220498

Variant2: c.1205G>A (p.W402X)

Variant2ClinVarID: 11908

Variant2CAID: CA220498

AdditionalVariants: N/A

ParentalGenotype: N/A

PreviouslyPublished N/A

Case#: Patient 8, born in 1994 (paper published in 2017), 9 months (age at first treatment), 2 years 3 months (age at last treatment)

DiseaseAssertion: MPSI-H

FamilyInfo: N/A

CasePresentingHPOs: Corneal clouding, retinopathy, cataract (HP:0007957, HP:0000488, HP:0000518)

CaseHPOFreeText: N/A

CaseNotHPOs: N/A

CaseNotHPOFreeText: N/A

CaseEnzymeAssay: 7.14 ng/mol (56.53 weight matched enzyme reference assay)

CaseUrineGAGs: 1.24 DS/CS

CaseERT: No

CaseBMT: Yes, Sib

Variant1: c.1205G>A (p.W402X)

Variant1ClinVarID: 11908

Variant1CAID: CA220498

Variant2: c.1205G>A (p.W402X)

Variant2ClinVarID: 11908

Variant2CAID: CA220498

AdditionalVariants: N/A

ParentalGenotype: N/A

PreviouslyPublished N/A

Case#: Patient 9, born in 2008 (paper published in 2017), 8 months (age at first treatment)

DiseaseAssertion: MPSI-H

FamilyInfo: N/A

CasePresentingHPOs: Corneal clouding (HP:0007957)

CaseHPOFreeText: N/A

CaseNotHPOs: Retinopathy, cataract (HP:0000488, HP:0000518)

CaseNotHPOFreeText: N/A

CaseEnzymeAssay: 47 ng/mol (32 weight matched enzyme reference assay)

CaseUrineGAGs: 0.34 DS/CS

CaseERT: Yes

CaseBMT: Yes, Cord

Variant1: c.1205G>A (p.W402X)

Variant1ClinVarID: 11908

Variant1CAID: CA220498

Variant2: c.208C>T (p.Q70X)

Variant2ClinVarID: 11909

Variant2CAID: CA204563

AdditionalVariants: N/A

ParentalGenotype: N/A

PreviouslyPublished N/A

Case#: Patient 3, born in 2005 (paper published in 2017), 2 years and 7 months (age at first treatment)

DiseaseAssertion: MPSI-H

FamilyInfo: N/A

CasePresentingHPOs: Corneal clouding (HP:0007957)

CaseHPOFreeText: N/A

CaseNotHPOs: Retinopathy, cataract (HP:0000488, HP:0000518)

CaseNotHPOFreeText: N/A

CaseEnzymeAssay: 86 ng/mol (60 weight matched enzyme reference assay)

CaseUrineGAGs: 0.43 DS/CS

CaseERT: Yes

CaseBMT: Yes, Sib

Variant1: c.17_24CCCGCGCC (Found to be c.17_24dup) (p.Ala9ProfsTer?)

Variant1ClinVarID: N/A

Variant1CAID: CA645372294

Variant2: c.1871A>T (p.Asp624Val)

Variant2ClinVarID: N/A

Variant2CAID: CA355965955

AdditionalVariants: N/A

ParentalGenotype: N/A

PreviouslyPublished N/A

Case#: Patient 11, born in 2003 (paper published in 2017), 1 year (age at first treatment)

DiseaseAssertion: MPSI-H

FamilyInfo: N/A

CasePresentingHPOs: Corneal clouding (HP:0007957)

CaseHPOFreeText: N/A

CaseNotHPOs: Retinopathy, cataract (HP:0000488, HP:0000518)

CaseNotHPOFreeText: N/A

CaseEnzymeAssay: 71.98 ng/mol (10.86 weight matched enzyme reference assay)

CaseUrineGAGs: 0.38 DS/CS

CaseERT: Yes

CaseBMT: Yes, Cord

Variant1: c.1205G>A (p.W402X)

Variant1ClinVarID: 11908

Variant1CAID: CA220498

Variant2: c.208C>T (p.Q70X)

Variant2ClinVarID: 11909

Variant2CAID: CA204563

AdditionalVariants: N/A

ParentalGenotype: N/A

PreviouslyPublished N/A

Case#: Family 4, Middle East

DiseaseAssertion: MPS1-H

FamilyInfo: N/A

CasePresentingHPOs: N/A

CaseHPOFreeText: The paper states that "Hurler form is characterized by skeletal abnormalities, hepatosplenomegaly and severe mental retardation" but is not specific to this patient.

CaseNotHPOs: N/A

CaseNotHPOFreeText: N/A

CaseEnzymeAssay: The α-L-iduronidase enzyme activities in leucocytes from all patients in the study was measured using the artificial substrate 4-methylumbelliferyl α-L iduronide (Sigma). Values ranged from 0 to 2.47 nmol/h/mg protein (reference range: 28–92 nmol/h/mg protein) and did not correlate to the clinical phenotype.

CaseUrineGAGs: N/A

CaseERT: N/A

CaseBMT: N/A

Variant1: c.1882C>T (p.R628X)

Variant1ClinVarID: 550421

Variant1CAID: CA2802462

Variant2: c.1882C>T (p.R628X)

Variant2ClinVarID: 550421

Variant2CAID: CA2802462

AdditionalVariants: N/A

ParentalGenotype: N/A

PreviouslyPublished N/A

Case#: Family 1, Middle East

DiseaseAssertion: MPS1-H

FamilyInfo: N/A

CasePresentingHPOs: N/A

CaseHPOFreeText: The paper states that "Hurler form is characterized by skeletal abnormalities, hepatosplenomegaly and severe mental retardation" but is not specific to this patient.

CaseNotHPOs: N/A

CaseNotHPOFreeText: N/A

CaseEnzymeAssay: The α-L-iduronidase enzyme activities in leucocytes from all patients in the study was measured using the artificial substrate 4-methylumbelliferyl α-L iduronide (Sigma). Values ranged from 0 to 2.47 nmol/h/mg protein (reference range: 28–92 nmol/h/mg protein) and did not correlate to the clinical phenotype.

α-L-iduronidase activity in COS-7 cells transiently transfected with wild-type or mutagenised cDNAs. α-L-iduronidase activity: 4.5 nmol/h/mg cell protein; values are the means of two experiments.

CaseUrineGAGs: N/A

CaseERT: N/A

CaseBMT: N/A

Variant1: c.623G>T (p.G208V)

Variant1ClinVarID: 3591555

Variant1CAID: CA355961949

Variant2: c.623G>T (p.G208V)

Variant2ClinVarID: 3591555

Variant2CAID: CA355961949

AdditionalVariants: N/A

ParentalGenotype: Parental testing conducted, each parent was shown to carry one of the sequence changes found in their affected child.

PreviouslyPublished N/A

Case#: Family 26, Pakistan

DiseaseAssertion: MPS1-S

FamilyInfo: N/A

CasePresentingHPOs: N/A

CaseHPOFreeText: The Scheie phenotype is characterized by aortic valve disease, corneal clouding, limited skeletal problems, but no mental retardation. This is a general assessment and not specific to this patient.

CaseNotHPOs: N/A

CaseNotHPOFreeText: N/A

CaseEnzymeAssay: The α-L-iduronidase enzyme activities in leucocytes from all patients in the study was measured using the artificial substrate 4-methylumbelliferyl α-L iduronide (Sigma). Values ranged from 0 to 2.47 nmol/h/mg protein (reference range: 28–92 nmol/h/mg protein) and did not correlate to the clinical phenotype.

α-L-iduronidase activity in COS-7 cells transiently transfected with wild-type or mutagenised cDNAs. α-L-iduronidase activity: 5.2 nmol/h/mg cell protein; values are the means of two experiments.

CaseUrineGAGs: N/A

CaseERT: N/A

CaseBMT: N/A

Variant1: c.956C>T (p.A319V)

Variant1ClinVarID: 1683230

Variant1CAID: CA2802126

Variant2: c.956C>T (p.A319V)

Variant2ClinVarID: 1683230

Variant2CAID: CA2802126

AdditionalVariants: N/A

ParentalGenotype: N/A

PreviouslyPublished N/A

Case#: Family 18, Slovenia

DiseaseAssertion: MPS1-H

FamilyInfo: N/A

CasePresentingHPOs: N/A

CaseHPOFreeText: The paper states that "Hurler form is characterized by skeletal abnormalities, hepatosplenomegaly and severe mental retardation" but is not specific to this patient.

CaseNotHPOs: N/A

CaseNotHPOFreeText: N/A

CaseEnzymeAssay: The α-L-iduronidase enzyme activities in leucocytes from all patients in the study was measured using the artificial substrate 4-methylumbelliferyl α-L iduronide (Sigma). Values ranged from 0 to 2.47 nmol/h/mg protein (reference range: 28–92 nmol/h/mg protein) and did not correlate to the clinical phenotype.

CaseUrineGAGs: N/A

CaseERT: N/A

CaseBMT: N/A

Variant1: c.652delC; c.740delC in the paper (old nomenclature)

Variant1ClinVarID: N/A

Variant1CAID: CA2586965939

Variant2: c.652delC; c.740delC in the paper (old nomenclature)

Variant2ClinVarID: N/A

Variant2CAID: CA2586965939

AdditionalVariants: N/A

ParentalGenotype: Parental testing conducted, each parent was shown to carry one of the sequence changes found in their affected child.

PreviouslyPublished N/A

Case#: Family 6, UK

DiseaseAssertion: MPS1-H

FamilyInfo: N/A

CasePresentingHPOs: N/A

CaseHPOFreeText: The paper states that "Hurler form is characterized by skeletal abnormalities, hepatosplenomegaly and severe mental retardation" but is not specific to this patient.

CaseNotHPOs: N/A

CaseNotHPOFreeText: N/A

CaseEnzymeAssay: The α-L-iduronidase enzyme activities in leucocytes from all patients in the study was measured using the artificial substrate 4-methylumbelliferyl α-L iduronide (Sigma). Values ranged from 0 to 2.47 nmol/h/mg protein (reference range: 28–92 nmol/h/mg protein) and did not correlate to the clinical phenotype.

CaseUrineGAGs: N/A

CaseERT: N/A

CaseBMT: N/A

Variant1: c.1205G>A (p.W402X)

Variant1ClinVarID: 11908

Variant1CAID: CA220498

Variant2: c.46_57del (p.Ser16_Ala19del); in the paper it is listed as c.134del12 (old nomenclature)

Variant2ClinVarID: 92643

Variant2CAID: CA220509

AdditionalVariants: N/A

ParentalGenotype: Parental testing conducted, each parent was shown to carry one of the sequence changes found in their affected child.

PreviouslyPublished N/A

Case#: Family 8, UK

DiseaseAssertion: MPS1-H

FamilyInfo: N/A

CasePresentingHPOs: N/A

CaseHPOFreeText: The paper states that "Hurler form is characterized by skeletal abnormalities, hepatosplenomegaly and severe mental retardation" but is not specific to this patient.

CaseNotHPOs: N/A

CaseNotHPOFreeText: N/A

CaseEnzymeAssay: The α-L-iduronidase enzyme activities in leucocytes from all patients in the study was measured using the artificial substrate 4-methylumbelliferyl α-L iduronide (Sigma). Values ranged from 0 to 2.47 nmol/h/mg protein (reference range: 28–92 nmol/h/mg protein) and did not correlate to the clinical phenotype.

CaseUrineGAGs: N/A

CaseERT: N/A

CaseBMT: N/A

Variant1: c.1205G>A (p.W402X)

Variant1ClinVarID: 11908

Variant1CAID: CA220498

Variant2: c.1855C>T (p.R619X)

Variant2ClinVarID: 280976

Variant2CAID: CA2802455

AdditionalVariants: N/A

ParentalGenotype: N/A

PreviouslyPublished N/A

Case#: Pt 1, age is 20 months (proband can be found in Table 1)

DiseaseAssertion: Hurler syndrome, mucopolysaccharidosis type IH, MPS IH, MPS type I

FamilyInfo: No family information provided

CasePresentingHPOs:

CaseHPOFreeText:

CaseNotHPOs:

CaseNotHPOFreeText:

CaseEnzymeAssay: In methods it is stated that an IDUA activity assay was conducted on cartilaginous pellets generated from patient-derived bone marrow stromal cells at 5 weeks. However, results of the IDUA activity assays are not stated.

CaseUrineGAGs: "Significantly higher levels of GAGs in MPS IH compared with HD pellets at.1 week of chondrogenic differentiation, thus indicating that GAG accumulation in MPS IH can be seen during cell condensation and early differentiation stages." Total GAG content for each sample in ug GAG/ug DNA shown in Figure 4 graphs.

CaseERT: Don't know

CaseBMT: Don't know

Variant1: p.Q70X

Variant1ClinVarID:

Variant1CAID: PA3044620172

Variant2: p.P496R

Variant2ClinVarID: 496861

Variant2CAID: CA2802275

AdditionalVariants: No additional variants mentioned

ParentalGenotype: No parental information provided

PreviouslyPublished: No mention of previously being published

Case#: Pt 7, age is 13 months (proband can be found in Table 1)

DiseaseAssertion: Hurler syndrome, mucopolysaccharidosis type IH, MPS IH, MPS type I

FamilyInfo: No family information provided

CasePresentingHPOs:

CaseHPOFreeText:

CaseNotHPOs:

CaseNotHPOFreeText:

CaseEnzymeAssay: In methods it is stated that an IDUA activity assay was conducted on cartilaginous pellets generated from patient-derived bone marrow stromal cells at 5 weeks. However, results of the IDUA activity assays are not stated.

CaseUrineGAGs: "Significantly higher levels of GAGs in MPS IH compared with HD pellets at.1 week of chondrogenic differentiation, thus indicating that GAG accumulation in MPS IH can be seen during cell condensation and early differentiation stages." Total GAG content for each sample in ug GAG/ug DNA shown in Figure 4 graphs.

CaseERT: Don't know

CaseBMT: Don't know

Variant1: p.Q70X

Variant1ClinVarID:

Variant1CAID: PA3044620172

Variant2: c.398_403del6

Variant2ClinVarID: 863830

Variant2CAID: CA2801912

AdditionalVariants: No additional variants mentioned

ParentalGenotype: No parental information provided

PreviouslyPublished: No mention of being previously published

Case#: Pt 4, age is 12 months (proband can be found in Table 1)

DiseaseAssertion: Hurler syndrome, mucopolysaccharidosis type IH, MPS IH, MPS type I

FamilyInfo: No family information provided

CasePresentingHPOs:

CaseHPOFreeText:

CaseNotHPOs:

CaseNotHPOFreeText:

CaseEnzymeAssay: In methods it is stated that an IDUA activity assay was conducted on cartilaginous pellets generated from patient-derived bone marrow stromal cells at 5 weeks. However, results of the IDUA activity assays are not stated.

CaseUrineGAGs: "Significantly higher levels of GAGs in MPS IH compared with HD pellets at.1 week of chondrogenic differentiation, thus indicating that GAG accumulation in MPS IH can be seen during cell condensation and early differentiation stages." Total GAG content for each sample in ug GAG/ug DNA shown in Figure 4 graphs.

CaseERT: Don't know

CaseBMT: Don't know

Variant1: p.P496R

Variant1ClinVarID: 496861

Variant1CAID: CA2802275

Variant2: p.P496R

Variant2ClinVarID: 496861

Variant2CAID: CA2802275

AdditionalVariants: No additional variants mentioned

ParentalGenotype: No parental information provided

PreviouslyPublished: No mention of previously being published

Case#: Family F proband, male, 1 year old (age of onset), Tunisia.

DiseaseAssertion: MPS1-H

FamilyInfo: Seven unaffected brothers with MPS1 (See results), parents were 2nd degree relatives (See Table 1)

CasePresentingHPOs: HP:0001433, HP:0001744, HP:0001999, (Hepatosplenomegaly, splenomegaly, abnormal facial shape)

CaseHPOFreeText: N/A

CaseNotHPOs: N/A

CaseNotHPOFreeText: N/A

CaseEnzymeAssay: IDUA activity (0.1 nmol/h/mg) (usual values: 1-5).

CaseUrineGAGs: glycosaminoglycans (102 mg/g of creatinine) (usual values: 9-46), abnormal electrophoresis profile with dermatan sulfate and heparan sulfate

CaseERT: N/A

CaseBMT: Yes

Variant1: c.1598C>G (p.P533R)

Variant1ClinVarID: 11910

Variant1CAID: CA256112

Variant2: c.1598C>G (p.P533R)

Variant2ClinVarID: 11910

Variant2CAID: CA256112

AdditionalVariants: N/A

ParentalGenotype: N/A

PreviouslyPublished N/A

Case#: 6, Male, 0.9 years (diagnosed), 13.0 years (report), 15 kg (weight), 102 cm (height), Iranian

DiseaseAssertion: Hurler Syndrome

FamilyInfo: Parents are consanguineous

CasePresentingHPOs: HP:0001249, HP:0001999, HP:0000943, HP:0001387, HP:0100790, HP:0000365, HP:0000238 (Mental Retardation, Facial Dysmorphic Features, Multiple Dysostosis, Joint Stiffness, Hernia, Deafness, Hydrocephalus)

CaseHPOFreeText: HM/HSM, Chronic Rhinorrhea

CaseNotHPOs: HP:0007957 (Corneal Capacity)

CaseNotHPOFreeText: Cardiac Manifestations

CaseEnzymeAssay: IDUA activity 1.3 (μmol/spot.20h)

CaseUrineGAGs: Quantitative urinary GAG 11.54 (mg/gCr)

CaseERT: N/A

CaseBMT: N/A

GenotypingMethod: Sanger Sequencing

Variant1: p.D301E

Variant2: N/A

AdditionalVariants: N/A

ParentalGenotype: N/A

PreviouslyPublished: N/A

Case#: 13, Male, 0.8 years (diagnosed), 1.6 years (report), 7.2 kg (weight), 71 cm (height), Iranian

DiseaseAssertion: Scheie Syndrome

FamilyInfo: Parents are not consanguineous

CasePresentingHPOs: HP:0001249, HP:0001999, HP:0100790 (Mental Retardation, Facial Dysmorphic Features, Hernia)

CaseHPOFreeText: HM/HSM, Chronic Rhinorrhea

CaseNotHPOs: HP:0000943, HP:0001387, HP:0000365, HP:0007957, HP:0000238 (Multiple Dysostosis, Joint Stiffness, Deafness, Corneal Opacity, Hydrocephalus)

CaseNotHPOFreeText: Cardiac Manifestations

CaseEnzymeAssay: IDUA activity 0.75 (μmol/spot.20h)

CaseUrineGAGs: Quantitative urinary GAG 7.4 (mg/gCr)

CaseERT: N/A

CaseBMT: N/A

GenotypingMethod: Sanger Sequencing

Variant1: p.S157P

Variant2: N/A

AdditionalVariants: N/A

ParentalGenotype: N/A

PreviouslyPublished: N/A

Case#: 21, Female, 0.8 years (diagnosed), 2.8 years (report), 7.5 kg (weight), 80 cm (height), Iranian

DiseaseAssertion: Hurler Syndrome

FamilyInfo: Parents are consanguineous

CasePresentingHPOs:HP:0001249, HP:0001999, HP:0000943, HP:0001387, HP:0100790, HP:0000365, HP:0007957, HP:0000238 (Mental Retardation, Facial Dysmorphic Features, Multiple Dysostosis, Joint Stiffness, Hernia, Deafness, Corneal Capacity, Hydrocephalus)

CaseHPOFreeText: HM/HSM, Chronic Rhinorrhea, Cardiac Manifestations (mitral stenosis)

CaseNotHPOs: N/A

CaseNotHPOFreeText: N/A

CaseEnzymeAssay: IDUA activity 0.98 (μmol/spot.20h)

CaseUrineGAGs: Quantitative urinary GAG 10.5 (mg/gCr)

CaseERT: N/A

CaseBMT: N/A

GenotypingMethod: Sanger Sequencing

Variant1: Not Provided

Variant2: N/A

AdditionalVariants: N/A

ParentalGenotype: N/A

PreviouslyPublished: N/A

Case#: 7, Female, 0.7 years (diagnosed), 12.9 years (report), 14.2 kg (weight), 97 cm (height), Iranian

DiseaseAssertion: Hurler-Scheie Syndrome

FamilyInfo: Parents are consanguineous

CasePresentingHPOs: HP:0001249, HP:0001999, HP:0000943, HP:0001387, HP:0100790, HP:0000365, HP:0000238 (Mental Retardation, Facial Dysmorphic Features, Multiple Dysostosis, Joint Stiffness, Hernia, Deafness, Hydrocephalus)

CaseHPOFreeText: HM/HSM, Chronic Rhinorrhea

CaseNotHPOs: HP:0007957 (Corneal Capacity)

CaseNotHPOFreeText: Cardiac Manifestations

CaseEnzymeAssay: IDUA activity 0.86 (μmol/spot.20h)

CaseUrineGAGs: Quantitative urinary GAG 10.11 (mg/gCr)

CaseERT: N/A

CaseBMT: N/A

GenotypingMethod: Sanger Sequencing

Variant1: p.G84R

Variant2: N/A

AdditionalVariants: N/A

ParentalGenotype: N/A

PreviouslyPublished: N/A

Variant 11 of 11

Variant1:NM_000203.3: c.613T>C p.(Cys205Arg)

Variant1CAID:CA355961926

Variant 10 of 11

Variant1:NM_000203.3: c.568_581del p.(Asn190Hisfs*204)

Variant1CAID:CA2801994

Variant 9 of 11

Variant1:NM_000203.3: c.494-1G>C

Variant1CAID:CA275298

PMID:35614200

Gene: IDUA

Disease: MPS1

Inheritance: Autosomal recessive

A list of 11 IDUA variants identified in cases with MPS is included in Supplemental Table 6, but the variants are not linked to specific patients and are listed individually (not as genotypes). A page note has been added for each variant.

Variant 8 of 11

Variant1:NM_000203.3: c.395T>C p.(Leu132Pro)

Variant1CAID:CA355961295