PMID: 29976218 Gene: IDUA Disease: MPS1 Inheritance: Autosomal recessive

Case#: 204 14.8 yrs male, age at initial diagnosis 5 yrs DiseaseAssertion: MPS IH-S FamilyInfo:Nil CasePresentingHPOs: CaseHPOFreeText: CaseNotHPOs: CaseNotHPOFreeText: CaseEnzymeAssay: IDUA activity: low leukocyte IDUA enzyme activity CaseUrineGAGs: CaseERT: 9 yrs on ERT, then study drug, valanafusp alpha, also called AGT-181 for 12 months

CaseBMT: No PreviouslyPublished Don't know Variant1:p.R48del Variant1ClinVarID: 1518010 Variant1CAID: Variant2:p.P533R Variant2ClinVarID: 11910 Variant2CAID: CA256112

Case#: Pt 105 , Age 30 years, Female, DiseaseAssertion: MPS1 Scheie syndrome. FamilyInfo: NA CasePresentingHPOs: NA CaseHPOFreeText: NA CaseNotHPOs: NA CaseNotHPOFreeText: NA

CaseEnzymeAssay: Low leukocyte IDUA enzyme activity CaseUrineGAGs: NA CaseERT: No CaseBMT: No Variant1: p.R383H Variant1ClinVarID: 558189 Variant1CAID: Variant2:p.W402X Variant2ClinVarID: 11908 Variant2CAID: CA220498 AdditionalVariants: NA ParentalGenotype: NA PreviouslyPublished:NA

Case#: Patient 1, male, Russian

DiseaseAssertion: MPS1-H

FamilyInfo: N/A

CasePresentingHPOs: Severe intellectual disability, corneal clouding, skeletal deformities, hepatosplenomegaly (HP:0010864, HP:0007957, HP:0000924, HP:0001433)

CaseHPOFreeText: N/A

CaseNotHPOs: N/A

CaseNotHPOFreeText: N/A

CaseEnzymeAssay: 4.5 nmol/mg/h (reference range 135 ± 57 nmol/mg/h)

CaseUrineGAGs: 42.9 mg GAG/mmol/creatinine (reference range 6.17 ± 3.79 mg GAG/mmol creatinine)

CaseERT: No

CaseBMT: No

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

Variant1ClinVarID: 11909

Variant1CAID: CA204563

Variant2: c.974insACCCCCATTTAC (p.Thr293_Tyr296dup) - in ClinVar this variant is listed as c.878_889dup12.

Variant2ClinVarID: 550382

Variant2CAID: CA2802114

AdditionalVariants: N/A

ParentalGenotype: N/A

PreviouslyPublished N/A

Case#: Patient 6, male, Russian

DiseaseAssertion: MPS1-H

FamilyInfo: N/A

CasePresentingHPOs: Severe intellectual disability, corneal clouding, skeletal deformities, hepatosplenomegaly (HP:0010864, HP:0007957, HP:0000924, HP:0001433)

CaseHPOFreeText: N/A

CaseNotHPOs: N/A

CaseNotHPOFreeText: N/A

CaseEnzymeAssay: 0.06 nmol/mg/h (reference range 135 ± 57 nmol/mg/h)

CaseUrineGAGs: 238.7 mg GAG/mmol/creatinine (reference range 6.17 ± 3.79 mg GAG/mmol creatinine)

CaseERT: No

CaseBMT: No

Variant1: c.1162dupA (p.Thr388Asnfs*11)

Variant1ClinVarID: N/A

Variant1CAID: CA2586965961

Variant2: c.1162dupA (p.Thr388Asnfs*11)

Variant2ClinVarID: N/A

Variant2CAID: CA2586965961

AdditionalVariants: N/A

ParentalGenotype: N/A

PreviouslyPublished N/A

Case#: Patient 44, Poland

DiseaseAssertion: MPS1-S

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.793G>C (p.G265R)

Variant2ClinVarID: 638074

Variant2CAID: CA2802098

AdditionalVariants: N/A

ParentalGenotype: N/A

PreviouslyPublished N/A

Case#: Patient 90, Turkey, patient belong to the same geographical region as patients 86, 92, and 98

DiseaseAssertion: MPS1-H

FamilyInfo: Parents belong to the same village

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.494-1G>A

Variant1ClinVarID: 557942

Variant1CAID: CA355961634

Variant2: c.494-1G>A

Variant2ClinVarID: 557942

Variant2CAID: CA355961634

AdditionalVariants: N/A

ParentalGenotype: N/A

PreviouslyPublished N/A

Case#: Patient 98, Turkey, patient belong to the same geographical region as patients 86, 90, and 92

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.494-1G>A

Variant1ClinVarID: 557942

Variant1CAID: CA355961634

Variant2: c.494-1G>A

Variant2ClinVarID: 557942

Variant2CAID: CA355961634

AdditionalVariants: N/A

ParentalGenotype: N/A

PreviouslyPublished N/A

Case#: Patient 2, Italy

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.979G>C (p.A327P)

Variant1ClinVarID: 167190

Variant1CAID: CA234128

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

Variant2ClinVarID: 167190

Variant2CAID: CA234128

AdditionalVariants: N/A

ParentalGenotype: N/A

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

PMID: 33389473

Gene: IDUA

Disease: MPS1

Inheritance: Autosomal recessive

Case#: Patient 30 (Table 3)

DiseaseAssertion: Severe naïve MPS 1

FamilyInfo: N/A

CasePresentingHPOs: N/A

CaseHPOFreeText: N/A

CaseNotHPOs: N/A

CaseNotHPOFreeText: N/A

CaseEnzymeAssay: 23 nmol/h/mg per DBS (dried blood spots) determined during NBS

CaseUrineGAGs: N/A

CaseERT: Yes

CaseBMT: N/A

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

Variant1ClinVarID: 11908

Variant1CAID: CA2204098

Variant2: c.1524+1G>T

Variant2ClinVarID: 555169

Variant2CAID: CA355964830

AdditionalVariants: N/A

ParentalGenotype: N/A

PreviouslyPublished N/A

Case#: Patient 21, 2 years old (age at report), male, Indian

DiseaseAssertion: MPS1-H

FamilyInfo: N/A

CasePresentingHPOs: Coarse facial features, hepatosplenomegaly, recurrent infections (HP:0000280, HP:0001433, HP:0002719)

CaseHPOFreeText: N/A

CaseNotHPOs: N/A

CaseNotHPOFreeText: N/A

CaseEnzymeAssay: 2.9% (Range of residual enzyme activity: 0.0%-4.8%)

CaseUrineGAGs: N/A

CaseERT: N/A

CaseBMT: N/A

Variant1: c.935G>A (p.Trp312Ter)

Variant1ClinVarID: N/A

Variant1CAID: CA355962697

Variant2: c.935G>A (p.Trp312Ter)

Variant2ClinVarID: N/A

Variant2CAID: CA355962697

AdditionalVariants: N/A

ParentalGenotype: N/A

PreviouslyPublished N/A

Case#: Patient 11, 4 years old (age at report), male, Indian

DiseaseAssertion: MPS1-H

FamilyInfo: Sibling of patient 10

CasePresentingHPOs: Coarse facial features, recurrent infections, dysostosis multiplex, intellectual disability, hernia (HP:0000280, HP:0002719, HP:0000943, HP:0001249, HP:0100790)

CaseHPOFreeText: N/A

CaseNotHPOs: N/A

CaseNotHPOFreeText: N/A

CaseEnzymeAssay: 3.6% (Range of residual enzyme activity: 0.0%-4.8%)

CaseUrineGAGs: N/A

CaseERT: N/A

CaseBMT: N/A

Variant1: c.531C>G (p.Phe177Leu)

Variant1ClinVarID: 2432729

Variant1CAID: CA2801983

Variant2: c.531C>G (p.Phe177Leu)

Variant2ClinVarID: 2432729

Variant2CAID: CA2801983

AdditionalVariants: N/A

ParentalGenotype: N/A

PreviouslyPublished N/A

Case#: Patient 39, 1 years old (age at report), male, Indian

DiseaseAssertion: MPS1-H

FamilyInfo: N/A

CasePresentingHPOs: Joint contractures, dysostosis multiplex (HP:0002828, HP:0000943)

CaseHPOFreeText: Cardiac disease

CaseNotHPOs: N/A

CaseNotHPOFreeText: N/A

CaseEnzymeAssay: 3.4% (Range of residual enzyme activity: 0.0%-4.8%)

CaseUrineGAGs: N/A

CaseERT: N/A

CaseBMT: N/A

Variant1: c.1373T>C (p.Leu458Pro)

Variant1ClinVarID: N/A

Variant1CAID: CA355964255

Variant2: c.1373T>C (p.Leu458Pro)

Variant2ClinVarID: N/A

Variant2CAID: CA355964255

AdditionalVariants: N/A

ParentalGenotype: N/A

PreviouslyPublished N/A

Case#: Patient 53, 2 years old (age at report), male, Indian

DiseaseAssertion: MPS1-H

FamilyInfo: N/A

CasePresentingHPOs: Coarse facial features, hepatosplenomegaly, corneal clouding, recurrent infections, intellectual disability, hernia (HP:0000280, HP:0001433, HP:0007957, HP:0002719, HP:0001249, HP:0100790)

CaseHPOFreeText: N/A

CaseNotHPOs: N/A

CaseNotHPOFreeText: N/A

CaseEnzymeAssay: 2.5% (Range of residual enzyme activity: 0.0%-4.8%)

CaseUrineGAGs: N/A

CaseERT: N/A

CaseBMT: N/A

Variant1: c.502G>T (p.Gly168Ter)

Variant1ClinVarID: N/A

Variant1CAID: CA355961652

Variant2: c.1402+1G>A

Variant2ClinVarID: 555490

Variant2CAID: CA355964379

AdditionalVariants: N/A

ParentalGenotype: N/A

PreviouslyPublished N/A

Case#: Patient 19, 1 years old (age at report), male, Indian

DiseaseAssertion: MPS1-H

FamilyInfo: N/A

CasePresentingHPOs: Coarse facial features, hepatosplenomegaly, joint contractures, corneal clouding, recurrent infections, dysostosis multiplex, hernia (HP:0000280, HP:0001433, HP:0002828, HP:0007957, HP:0002719, HP:0000943, HP:0100790)

CaseHPOFreeText: Cardiac disease

CaseNotHPOs: N/A

CaseNotHPOFreeText: N/A

CaseEnzymeAssay: 2.7% (Range of residual enzyme activity: 0.0%-4.8%)

CaseUrineGAGs: N/A

CaseERT: N/A

CaseBMT: N/A

Variant1: c.784delC (p.His262Thrfs*55)

Variant1ClinVarID: 956890

Variant1CAID: CA2802083

Variant2: c.784delC (p.His262Thrfs*55)

Variant2ClinVarID: 956890

Variant2CAID: CA2802083

AdditionalVariants: N/A

ParentalGenotype: N/A

PreviouslyPublished N/A

Case#: Patient 49, 2 years old (age at report), male, Indian

DiseaseAssertion: MPS1-H

FamilyInfo: N/A

CasePresentingHPOs: Coarse facial features, hepatosplenomegaly, recurrent infections, dysostosis multiplex, hernia (HP:0000280, HP:0001433, HP:0002719, HP:0000943, HP:0100790)

CaseHPOFreeText: N/A

CaseNotHPOs: N/A

CaseNotHPOFreeText: N/A

CaseEnzymeAssay: 2.7% (Range of residual enzyme activity: 0.0%-4.8%)

CaseUrineGAGs: N/A

CaseERT: N/A

CaseBMT: N/A

Variant1: c.(1189+1)(1190–1)(1959_?)del in the paper, unsure how to write this in current nomenclature.

Variant1ClinVarID: N/A

Variant1CAID: N/A

Variant2: c.(1189+1_1190-1)(2003?)del in the paper, unsure how to write this in current nomenclature.

Variant2ClinVarID: N/A

Variant2CAID: N/A

AdditionalVariants: N/A

ParentalGenotype: N/A

PreviouslyPublished N/A

Case#: Patient 47, 2 years old (age at report), female, Indian

DiseaseAssertion: MPS1-H

FamilyInfo: N/A

CasePresentingHPOs: N/A

CaseHPOFreeText: N/A

CaseNotHPOs: N/A

CaseNotHPOFreeText: N/A

CaseEnzymeAssay: 1.8% (Range of residual enzyme activity: 0.0%-4.8%)

CaseUrineGAGs: N/A

CaseERT: N/A

CaseBMT: N/A

Variant1: c.(792+1_793-1)_(972+1_973-1)del in the paper, unsure how to write this in current nomenclature.

Variant1ClinVarID: N/A

Variant1CAID: N/A

Variant2: c.(792+1_793-1)_(972+1_973-1)del in the paper, unsure how to write this in current nomenclature.

Variant2ClinVarID: N/A

Variant2CAID: N/A

AdditionalVariants: N/A

ParentalGenotype: N/A

PreviouslyPublished N/A

Case#: Patient 46, 9 years old (age at report), female, Indian

DiseaseAssertion: MPS1-H

FamilyInfo: N/A

CasePresentingHPOs: Coarse facial features, hepatosplenomegaly, joint contractures (HP:0000280, HP:0001433, HP:0002828)

CaseHPOFreeText: N/A

CaseNotHPOs: N/A

CaseNotHPOFreeText: N/A

CaseEnzymeAssay: 0.0% (Range of residual enzyme activity: 0.0%-4.8%)

CaseUrineGAGs: N/A

CaseERT: N/A

CaseBMT: N/A

Variant1: c.1898C>T (p.Ser633Leu)

Variant1ClinVarID: 556406

Variant1CAID: CA355966010

Variant2: c.1898C>T (p.Ser633Leu)

Variant2ClinVarID: 556406

Variant2CAID: CA355966010

AdditionalVariants: N/A

ParentalGenotype: N/A

PreviouslyPublished N/A

Case#: Patient 36, 6 years old (age at report), male, Indian

DiseaseAssertion: MPS1-H

FamilyInfo: N/A

CasePresentingHPOs: Coarse facial features, hepatosplenomegaly, joint contractures, corneal clouding, recurrent infections, dysostosis multiplex, intellectual disability, hernia (HP:0000280, HP:0001433, HP:0002828, HP:0007957, HP:0002719, HP:0000943, HP:0001249, HP:0100790)

CaseHPOFreeText: N/A

CaseNotHPOs: N/A

CaseNotHPOFreeText: N/A

CaseEnzymeAssay: 2.5% (Range of residual enzyme activity: 0.0%-4.8%)

CaseUrineGAGs: N/A

CaseERT: N/A

CaseBMT: N/A

Variant1: c.1373T>C (p.Leu458Pro)

Variant1ClinVarID: N/A

Variant1CAID: CA355964255

Variant2: c.1373T>C (p.Leu458Pro)

Variant2ClinVarID: N/A

Variant2CAID: CA355964255

AdditionalVariants: N/A

ParentalGenotype: N/A

PreviouslyPublished N/A

PMID: 8328452

Gene: IDUA

Disease: MPS1

Inheritance: Autosomal recessive

Case#: Patient M3, Muslim religious group, located in Gaza. The cells of the patient were listed in the catalog of the Human Genetic Mutant Cell Repository as "Hurler/Scheie". However, the patient at age 6 years had been described as having a typical MPS1-H phenotype except for apparently normal intelligence (measured across a language barrier).

DiseaseAssertion: MPS1-H/S or MPS1-H

FamilyInfo: Parents were found to have both mutations were found in heterozygous form in the DNA. Affected brother deceased at age 9.

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.1225G>A (p.G409R)

Variant1ClinVarID: 1084956

Variant1CAID: CA91169920

Variant2: (p.X654C)

Variant2ClinVarID: N/A

Variant2CAID: N/A

AdditionalVariants: N/A

ParentalGenotype: N/A

PreviouslyPublished N/A

Case#: Patient D1, Druze religious group, located in lower Galilee.

DiseaseAssertion: MPS1-H

FamilyInfo: Both parents, as well as an aunt and uncle who had a deceased affected child, were heterozygous for the same mutation.

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.192C>A (p.Y64X)

Variant1ClinVarID: 11914

Variant1CAID: N/A

Variant2: N/A

Variant2ClinVarID: N/A

Variant2CAID: N/A

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#: Functional assay variant with a clinical significance of being a VUS. Variant not found in patients but generated to compare with p.L526P

DiseaseAssertion: MPS-I

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.1576C>A (p.L326M)

Variant1ClinVarID: N/A

Variant1CAID: CA355964993

Variant2: N/A

Variant2ClinVarID: N/A

Variant2CAID: N/A

AdditionalVariants: N/A

ParentalGenotype: N/A

PreviouslyPublished N/A

Case#: Functional assay variant with a clinical significance of clinically benign.

DiseaseAssertion: MPS-I

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.235G>A (p.A79T)

Variant1ClinVarID: 195038

Variant1CAID: CA201508

Variant2: N/A

Variant2ClinVarID: N/A

Variant2CAID: N/A

AdditionalVariants: N/A

ParentalGenotype: N/A

PreviouslyPublished N/A

Case#: Functional assay variant with a clinical significance of being likely pathogenic.

DiseaseAssertion: MPS-I

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.1709A>T (p.D570V)

Variant1ClinVarID: 1980496

Variant1CAID: CA355965255

Variant2: N/A

Variant2ClinVarID: N/A

Variant2CAID: N/A

AdditionalVariants: N/A

ParentalGenotype: N/A

PreviouslyPublished N/A

Case#: Functional assay variant with a clinical significance of being a VUS.

DiseaseAssertion: MPS-I

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.298A>G (p.R100G)

Variant1ClinVarID: 2058952

Variant1CAID: CA2801159

Variant2: N/A

Variant2ClinVarID: N/A

Variant2CAID: N/A

AdditionalVariants: N/A

ParentalGenotype: N/A

PreviouslyPublished N/A

Case#: Functional assay variant with a clinical significance of having conflicting interpretations.

DiseaseAssertion: MPS-I

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.757G>T (p.G253C)

Variant1ClinVarID: 554213

Variant1CAID: CA2802076

Variant2: N/A

Variant2ClinVarID: N/A

Variant2CAID: N/A

AdditionalVariants: N/A

ParentalGenotype: N/A

PreviouslyPublished N/A

Case#: Patient 2662, northern European origin, 11 years old (age of diagnosis), 22 years old (age at report), male, attended special schools until 15 years old, has not attained the ability to read and write, and has an increasingly poor memory.

DiseaseAssertion: MPS-1H/S, intermediate

FamilyInfo: Two affected younger sisters with MPS1 who presumably have the same R89Q/1060+2t-*-c genotype. he youngest sister died of bronchopneumonia at 22 mo of age. His second sister presented at 2 years and 6 mo of age with good general health, apart from upper respiratory tract infection, coarse facial features, enlarged liver and spleen, and limitation of elbow extension. This sister is now 20 years of age, has coarse facial features and joint limitations, is obese, and has a short stature. She is "bright" and able to live in her own flat with visiting help.

CasePresentingHPOs: Intellectual disability, memory impairment, limited motor development, severe joint contractures, short stature, obesity, macrocephaly, coarse facial features, hearing impairment, visual impairment (HP:0001249, HP:0002354, HP:0002194, HP:0002828, HP:0004322, HP:0001513, HP:0000256, HP:0000280, HP:0000365, HP:0000505)

CaseHPOFreeText: N/A

CaseNotHPOs: N/A

CaseNotHPOFreeText: N/A

CaseEnzymeAssay: Fibroblasts with two monoclonal antibodies detected 7%-10% of the normal levels of IDUA protein compared with only 1.5% of IDUA protein in a R89Q/W402X compound heterozygote

CaseUrineGAGs: N/A

CaseERT: N/A

CaseBMT: N/A

Variant1: c.266G>A (p.R89Q)

Variant1ClinVarID: 11922

Variant1CAID: CA256124

Variant2: c.972+2T>C (1060+2T>C)

Variant2ClinVarID: N/A

Variant2CAID: CA355962890

AdditionalVariants: N/A

ParentalGenotype: N/A

PreviouslyPublished N/A

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

Case#: Bach Patient D2, Israel, Druze

DiseaseAssertion: MPS I, Hurler

FamilyInfo: parents are het carriers

CasePresentingHPOs:

CaseHPOFreeText: Severe disease described as: "manifested from late infancy by dysostosis multiplex, coarse facies, corneal opacities, cardiovascular disease, hepatosplenomegaly, joint stiffness, and mental retardation; death usually occurs in the first decade of life." However, no specific information provided about proband. Level of mRNA in patient fibroblasts was half that of the normal control after normalization for beta-actin

CaseNotHPOs:

CaseNotHPOFreeText:

GenotypingMethod: PCR amplification of reverse-transcribed RNA or genomic DNA segments, cycle sequencing of PCR products, and restriction-enzyme analysis

PreviouslyPublished: preliminary account of this data summarized in a previous abstract: PMID: 8477267

Variant: Gln310Ter homozygous

CAID: CA256115

SupplementalData: n/a

Case#: Patient I, origin of patient is Germany/Italy

DiseaseAssertion: Hurler syndrome (H)

FamilyInfo: No family information stated in this paper

CasePresentingHPOs:

CaseHPOFreeText:

CaseNotHPOs:

CaseNotHPOFreeText:

CaseEnzymeAssay: 0 nmol/mghour IDUA enzyme activity in patient. Reference range of IDUA enzyme is 0.27 - 9.00 nmol/mghour. These results obtained from leucocyte

CaseUrineGAGs: Information not stated in this paper

CaseERT: Don't know

CaseBMT: Don't know

Variant1: c.973‐7C>G

Variant1ClinVarID:

Variant1CAID: CA2586965950

Variant2: Not identified in this study

Variant2ClinVarID: N/A

Variant2CAID: N/A

AdditionalVariants: No additional variants mentioned

ParentalGenotype: No parental information provided

PreviouslyPublished: States that this variant is reported in this paper for the first time, therefore I do not believe the patient has been previously published

Case#: Patient 14, male, 10 years (age at presentation).

DiseaseAssertion: MPS1-H/S

FamilyInfo: Consanguinity in the family not present for this patient.

CasePresentingHPOs: Corneal clouding, coarse facial features, dystosis multiplex, hepatomegaly, joint contractures, short stature (HP:0007957, HP:0000256, HP:0000943, HP:0002240, HP:0100790, HP:0004322)

CaseHPOFreeText: N/A

CaseNotHPOs: N/A

CaseNotHPOFreeText: N/A

CaseEnzymeAssay: N/A

CaseUrineGAGs: N/A

CaseERT: N/A

CaseBMT: N/A

Variant1: c.158+5delinsAA

Variant1ClinVarID: N/A

Variant1CAID: CA2586973515

Variant2: c.895G>T (p.E299X)

Variant2ClinVarID: 987878

Variant2CAID: CA355962511

AdditionalVariants: N/A

ParentalGenotype: Father was a carrier for c.158+5delGClinsAA (also written as c.158+5delinsAA); mother was a carrier for c.895G>T

PreviouslyPublished N/A

Case#: Patient 18, male, 2 years (age at presentation).

DiseaseAssertion: MPS1-H

FamilyInfo: Consanguinity in the family present for this patient.

CasePresentingHPOs: Corneal clouding, coarse facial features, dystosis multiplex, global developmental delay, hepatomegaly, joint stiffness, Mongolian blue spots, splenomegaly (HP:0007957, HP:0000256, HP:0000943, HP:0001263, HP:0002240, HP:0001387, HP:0011369, HP:0001744)

CaseHPOFreeText: N/A

CaseNotHPOs: N/A

CaseNotHPOFreeText: N/A

CaseEnzymeAssay: N/A

CaseUrineGAGs: N/A

CaseERT: N/A

CaseBMT: N/A

Variant1: c.1096_1099delACCG (p.Thr366Argfs*73)

Variant1ClinVarID: 1065522

Variant1CAID: CA2499217017

Variant2: c.1096_1099delACCG (p.Thr366Argfs*73)

Variant2ClinVarID: 1065522

Variant2CAID: CA2499217017

AdditionalVariants: N/A

ParentalGenotype: N/A

PreviouslyPublished N/A

Case#: Patient 9, female, 1 year (age at presentation).

DiseaseAssertion: MPS1-H

FamilyInfo: Consanguinity in the family present for this patient.

CasePresentingHPOs: Corneal clouding, coarse facial features, dysostosis multiplex, global developmental delay, hepatomegaly, joint stiffness, splenomegaly, recurrent respiratory infections, umbilical hernia (HP:0007957, HP:0000256, HP:0000943, HP:0001263, HP:0002240, HP:0001387, HP:0001744, HP:0002205, HP:0001537)

CaseHPOFreeText: N/A

CaseNotHPOs: N/A

CaseNotHPOFreeText: N/A

CaseEnzymeAssay: N/A

CaseUrineGAGs: N/A

CaseERT: N/A

CaseBMT: N/A

Variant1: c.362T>C (p.L121P)

Variant1ClinVarID: 1343382

Variant1CAID: CA355961174

Variant2: c.362T>C (p.L121P)

Variant2ClinVarID: 1343382

Variant2CAID: CA355961174

AdditionalVariants: N/A

ParentalGenotype: N/A

PreviouslyPublished N/A

Case#: Patient 7, male, 1 month (age at presentation).

DiseaseAssertion: MPS1-H

FamilyInfo: Consanguinity in the family not present for this patient. Family conducted a prenatal diagnosis on the next pregnancy and CVS to be unaffected

CasePresentingHPOs: Corneal clouding, coarse facial features, dysostosis multiplex, global developmental delay, hepatomegaly, joint stiffness, splenomegaly, umbilical hernia (HP:0007957, HP:0000256, HP:0000943, HP:0001263, HP:0002240, HP:0001387, HP:0001744, HP:0001537)

CaseHPOFreeText: N/A

CaseNotHPOs: N/A

CaseNotHPOFreeText: N/A

CaseEnzymeAssay: N/A

CaseUrineGAGs: N/A

CaseERT: N/A

CaseBMT: N/A

Variant1: c.362T>C (p.L121P)

Variant1ClinVarID: 1343382

Variant1CAID: CA355961174

Variant2: c.362T>C (p.L121P)

Variant2ClinVarID: 1343382

Variant2CAID: CA355961174

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

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

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#: Infant 4

DiseaseAssertion: N/A

FamilyInfo: Has an older sibling who is asymptomatic, has normal urine GAGs, and shares the same genotype.

CasePresentingHPOs: N/A

CaseHPOFreeText: N/A

CaseNotHPOs: N/A

CaseNotHPOFreeText: N/A

CaseEnzymeAssay: 0.2 nmol/h/mg; normal range, 6-71.4 nmol/h/mg

CaseUrineGAGs: 18.61 mg/mmol creatinine; normal ranges, 0-53 mg/mmol creatinine. Heparan sulfate was slightly elevated at 7.46 g/mol creatinine (normal, 0-5.71 g/mol creatinine) in 2 separate specimens.

CaseERT: N/A

CaseBMT: N/A

Variant1: c.720C>G (p.H240Q)

Variant1ClinVarID: 1011483

Variant1CAID: CA355962130

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

Variant2ClinVarID: 1470032

Variant2CAID: CA355963356

AdditionalVariants: N/A

ParentalGenotype: c.720C>G (maternal); c.1112T>A (paternal)

PreviouslyPublished N/A

Case#: Infant 1

DiseaseAssertion: N/A

FamilyInfo: N/A

CasePresentingHPOs: N/A

CaseHPOFreeText: N/A

CaseNotHPOs: N/A

CaseNotHPOFreeText: N/A

CaseEnzymeAssay: 5.1 nmol/h/mg; normal range, 15.1-50.9 nmol/h/mg

CaseUrineGAGs: 22.6 mg/mmol creatinine; normal ranges, 0-53 mg/mmol creatinine

CaseERT: N/A

CaseBMT: N/A

Variant1: c.298A>G (p.R100G)

Variant1ClinVarID: 2058952

Variant1CAID: CA2801159

Variant2: c.300-20C>T

Variant2ClinVarID: 1415135

Variant2CAID: CA2801857

AdditionalVariants: c.1345C>A (p.H449N)

ParentalGenotype: c.298A>G (maternal); c.300-20C>T (paternal); c.1345C>A (paternal)

PreviouslyPublished N/A

Case#: Patient 4 was biochemically diagnosed with MPS I because they showed an increase in urinary GAGs and a reduction in IDUA activity in leukocytes. Patient 4 was diagnosed at 2 years and 7 months.

DiseaseAssertion: MPSI-H/S

FamilyInfo: N/A

CasePresentingHPOs: Coarse facies, corneal clouding, hernias, skeletal abnormalities, cardiac abnormalities, and hepatosplenomegaly (HP:0000256, HP:0007957, HP:0100790, HP:0002360, HP:0001627, HP:0001433)

CaseHPOFreeText: N/A

CaseNotHPOs: Intellectual disability, growth delay (HP:0001249, HP:0001510)

CaseNotHPOFreeText: N/A

CaseEnzymeAssay: IDUA activity of 6.5 nmol/mg/protein/hr. No reference range provided.

CaseUrineGAGs: 202.8 CPC unit/g creatinine. No reference range provided.

CaseERT: N/A

CaseBMT: N/A

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

Variant1ClinVarID: 1458769

Variant1CAID: CA356987

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

Variant2ClinVarID: 550421

Variant2CAID: CA2802462

AdditionalVariants: N/A

ParentalGenotype: N/A

PreviouslyPublished N/A

Case#: P4-IDUA, F, European, Italy DiseaseAssertion: MPS1 - Pseudo/VUS FamilyInfo: CasePresentingHPOs: CaseHPOFreeText: CaseNotHPOs: CaseNotHPOFreeText: CaseEnzymeAssay: NBS 1.4 triplex / 3.8 single CaseUrineGAGs: CaseERT: CaseBMT: Variant1: c.246C>G Variant1ClinVarID: 92637 Variant1CAID: CA220506 Variant2: c.1716C>G Variant2ClinVarID: 1431214 Variant2CAID: CA355965272 AdditionalVariants: ParentalGenotype: PreviouslyPublished

Case#: P2-IDUA, M, North Africa, Morocco DiseaseAssertion: MPS1 - Psuedu/VUS FamilyInfo: CasePresentingHPOs: CaseHPOFreeText: CaseNotHPOs: CaseNotHPOFreeText: CaseEnzymeAssay: NBS 0.96 triplex / 4.2 single CaseUrineGAGs: CaseERT: CaseBMT: Variant1: c.246C>G Variant1ClinVarID: 92637 Variant1CAID: 92637 Variant2: c.1757C>T Variant2ClinVarID: 571910 Variant2CAID: CA2802396 AdditionalVariants: ParentalGenotype: PreviouslyPublished

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#: 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#:3. 0.7 year Male, diagnosed at 0.4 years DiseaseAssertion:MPS1H FamilyInfo:NA CasePresentingHPOs:NA CaseHPOFreeText:NA CaseNotHPOs:NA CaseNotHPOFreeText:NA CaseEnzymeAssay:Undetectable CaseUrineGAGs:NA CaseERT:NA CaseBMT:Yes, Unrelated cord blood, Post HSCT 18.2 nmol/h/mg of protein ( α-l-Iduronidase Levels) Variant1:IDUA : c.178C>T Variant1ClinVarID:655054 Variant1CAID: Variant2:IDUA: c.1205G>A Variant2ClinVarID: 11908 Variant2CAID:CA220498 AdditionalVariants: ParentalGenotype: PreviouslyPublished

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

PMID: 19954743

Gene: IDUA

Disease: MPS1

Inheritance: Autosomal recessive

Case#: MPS 1 patient

DiseaseAssertion: N/A

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.943G>T (p.D315Y)

Variant2ClinVarID: 4539822

Variant2CAID: CA355962740

AdditionalVariants: N/A

ParentalGenotype: N/A

PreviouslyPublished N/A

Case#: Patient 3, 4 years old, Iranian

DiseaseAssertion: MPS1-H (Severe)

FamilyInfo: N/A

CasePresentingHPOs: N/A

CaseHPOFreeText: N/A

CaseNotHPOs: N/A

CaseNotHPOFreeText: N/A

CaseEnzymeAssay: IDUA activity not detected

CaseUrineGAGs: N/A

CaseERT: N/A

CaseBMT: N/A

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

PMID: 31544795

Gene: IDUA

Disease: MPS1

Inheritance: Autosomal recessive

Case#: Patient No. 5 (Table 1), Black race, male, 2.84 years old (age at time of gene therapy), 77 IQ score, 2.18 years since gene therapy (2 years since latest visit). An acute hypersensitivity reaction that occurred in Patient 5 on day 12 after HSPC gene therapy and concomitantly to a first administration of vancomycin was considered by the investigators to be probably related to HSPC gene therapy. The event resolved promptly after treatment with antihistamines, intravenous fluids, and glucocorticoids, with no sequelae.

DiseaseAssertion: MPS-IH

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

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

Variant1ClinVarID: 11908

Variant1CAID: CA220498

Variant2: c.1409delT (p.V470AfsX?)

Variant2ClinVarID: N/A

Variant2CAID: N/A

AdditionalVariants: N/A

ParentalGenotype: N/A

PreviouslyPublished N/A

Case#: CA-106 ID number, Table S1.1 of Supplementary Material. Male, 5 months old (age at first symptoms), 6.5 months old (age at diagnosis). Stored frozen (-20ºC) 1.3 yr

DiseaseAssertion: Severe MPS-I

FamilyInfo: N/A

CasePresentingHPOs: N/A

CaseHPOFreeText: Bump on back, chronic breathing problems, moderate-severe hearing loss.

CaseNotHPOs: N/A

CaseNotHPOFreeText: N/A

CaseEnzymeAssay: N/A

CaseUrineGAGs: 1351 fmol/punch

CaseERT: N/A

CaseBMT: Yes - In April 2018

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#: CA-120 ID number, Table S1.1 of Supplementary Material. Female, 8 months old (age at first symptoms), 9 years and 6 months old (age at diagnosis). Stored frozen (-20ºC) 28 yr. May be the sibling of CA-119 due to closeness in ID numbers as well as having the same variants.

DiseaseAssertion: Attenuated MPS-I

FamilyInfo: N/A

CasePresentingHPOs: Ear infections (12 sets of tubes), hernia, joint contractures (HP:0410018, HP:0100790, HP:0100790)

CaseHPOFreeText: Perri Robin Syndrome, Adenoids removed (2x). Heart Valves, Spine, Contractures (No additional information provided about these symptoms).

CaseNotHPOs: N/A

CaseNotHPOFreeText: N/A

CaseEnzymeAssay: N/A

CaseUrineGAGs: 399 fmol/punch

CaseERT: N/A

CaseBMT: N/A

Variant1: c.1651-7C>T

Variant1ClinVarID: 1147380

Variant1CAID: CA438057995

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

Variant2ClinVarID: 11908

Variant2CAID: CA220498

AdditionalVariants: N/A

ParentalGenotype: N/A

PreviouslyPublished N/A

PMID: 33098355

Gene: IDUA

Disease: MPS1

Inheritance: Autosomal recessive

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#: 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