Case#: Patient 1, Egyptian, female, 1.5 years old

DiseaseAssertion: MPS1-H

FamilyInfo: Parents were 1st cousins

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.766del (c.854delC is the nomenclature in the literature but it is not current)

Variant1ClinVarID: N/A

Variant1CAID: CA2499922676

Variant2: c.766del (c.854delC is the nomenclature in the literature but it is not current)

Variant2ClinVarID: N/A

Variant2CAID: CA2499922676

AdditionalVariants: IVS5 (1486)C>T - this is not the current nomenclature but it is identified as a polymorphism in the article. c.1398C>T seems to be the current nomenclature for this variant.

ParentalGenotype: All mutations were confirmed in the parental DNA

PreviouslyPublished N/A

Case#: Patient 7, 6 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

Case#: Infant #1, female

DiseaseAssertion: MPS-I

FamilyInfo: N/A

CasePresentingHPOs: N/A

CaseHPOFreeText: N/A

CaseNotHPOs: N/A

CaseNotHPOFreeText: N/A

CaseEnzymeAssay: 1.20 IDUA enzyme activity (Ref. 5.9–27.8 μmol/g protein/h)

CaseUrineGAGs: DMB/Cre. Ratio - 37.86, DS - 0.27, HS - 0.10, KS - 5.69 GAG quantifications (DMB/Cre ratio) and the normal reference values based on the age groups: <6 mos: <70.68 mg /mmol cre.; 6 mos–2 yrs: <46.80 mg /mmol cre.; 2–17 yrs: <20.98 mg /mmol cre.; and >18 yrs: <12.62 mg /mmol cre. Quantitative analyses of GAG-derived disaccharides (DS, S, or KS) by tandem mass spectrometry assay. The normal cut-off values: DS < 0.80 μg/mL; HS < 0.78 μg/mL; and KS < 7.90 μg/mL.

CaseERT: N/A

CaseBMT: N/A

Variant1: c.343G>A (p.Asp115Asn)

Variant1ClinVarID: N/A

Variant1CAID: CA355961124

Variant2: c.2T>C (p.M1?)

Variant2ClinVarID: 639529

Variant2CAID: CA2801095

AdditionalVariants: N/A

ParentalGenotype: N/A

PreviouslyPublished N/A

Case#: Patient 19 (see Table 2), 38 weeks (Gestational age)

DiseaseAssertion: MPS1-H/S

FamilyInfo: Sibling of Patient 20 (see Table 2)

CasePresentingHPOs: N/A

CaseHPOFreeText: N/A

CaseNotHPOs: Inguinal hernia (HP:0000023)

CaseNotHPOFreeText: Upper respiratory tract involvement

CaseEnzymeAssay: 0.92 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 3 (see Table 2), 40 weeks (Gestational age)

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.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 24 (see Table 2), 40 weeks (Gestational age)

DiseaseAssertion: MPS1-S

FamilyInfo: N/A

CasePresentingHPOs: N/A

CaseHPOFreeText: N/A

CaseNotHPOs: Inguinal hernia (HP:0000023)

CaseNotHPOFreeText: Upper respiratory tract involvement

CaseEnzymeAssay: 1.05 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.1148G>A (p.R383H)

Variant2ClinVarID: 558189

Variant2CAID: CA:2802205

AdditionalVariants: N/A

ParentalGenotype: N/A

PreviouslyPublished N/A

Case#: Subject 5, female in her 20s (age at enrollment)

DiseaseAssertion: MPS1-HS

FamilyInfo: N/A

CasePresentingHPOs: HP:0002176 (Spinal cord compression)

CaseHPOFreeText: Improved balance, decreased spasticity

CaseNotHPOs: N/A

CaseNotHPOFreeText: N/A

CaseEnzymeAssay: N/A

CaseUrineGAGs: N/A

CaseERT: Yes - Enzyme replacement therapy with laronidase, showed no worsening in symptoms of spinal cord compression or neurologic findings.

CaseBMT: N/A

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

Variant1ClinVarID: 11909

Variant1CAID: CA204563

Variant2: c.396insAC - variant not known; an option could be c.397_398insCA

Variant2ClinVarID: N/A

Variant2CAID: N/A

AdditionalVariants: N/A

ParentalGenotype: N/A

PreviouslyPublished N/A

Case#: Patient 31, 6 years old (age at report), male, Indian

DiseaseAssertion: MPS1-H

FamilyInfo: Sibling of Patient 32

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: N/A

CaseNotHPOs: N/A

CaseNotHPOFreeText: N/A

CaseEnzymeAssay: 3.0% (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 12, 7 years old (age at report), female, Indian

DiseaseAssertion: MPS1-H

FamilyInfo: N/A

CasePresentingHPOs: Coarse facial features, hepatosplenomegaly, joint contractures, intellectual disability (HP:0000280, HP:0001433, HP:0002828, HP:0001249)

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.532G>A (p.Glu178Lys)

Variant1ClinVarID: 2203495

Variant1CAID: CA355961709

Variant2: c.532G>A (p.Glu178Lys)

Variant2ClinVarID: 2203495

Variant2CAID: CA355961709

AdditionalVariants: N/A

ParentalGenotype: N/A

PreviouslyPublished N/A

Case#: Patient 23, 9 months old (age at report), female, Indian

DiseaseAssertion: MPS1-H

FamilyInfo: N/A

CasePresentingHPOs: Intellectual disability (HP:0001249)

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.1029C>A (p.Tyr353Ter)

Variant1ClinVarID: 222997

Variant1CAID: CA356984

Variant2: c.1029C>A (p.Tyr353Ter)

Variant2ClinVarID: 222997

Variant2CAID: CA356984

AdditionalVariants: N/A

ParentalGenotype: N/A

PreviouslyPublished N/A

Case#: Patient 14, 5 years old (age at report), male, Indian

DiseaseAssertion: MPS1-H

FamilyInfo: N/A

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

CaseHPOFreeText: Cardiac disease

CaseNotHPOs: N/A

CaseNotHPOFreeText: N/A

CaseEnzymeAssay: 2.8% (Range of residual enzyme activity: 0.0%-4.8%)

CaseUrineGAGs: N/A

CaseERT: N/A

CaseBMT: N/A

Variant1: c.543T>G (p.Asn181Lys)

Variant1ClinVarID: N/A

Variant1CAID: CA355961734

Variant2: c.543T>G (p.Asn181Lys)

Variant2ClinVarID: N/A

Variant2CAID: CA355961734

AdditionalVariants: N/A

ParentalGenotype: N/A

PreviouslyPublished N/A

Case#: Patient 6 (see Table 1), 25 years old - deceased (age at report), 9 months old (age at onset), male, height of 120 cm, weight of 20 kg, location at Djerba: Land

DiseaseAssertion: MPS1 - intermediate

FamilyInfo: One affected siblings (Patient 7), parents were 1st cousins (see Table 2), parents have the same grandfather but with a different wife (see Table 4), aged 40 yrs (M) and 49 yrs (F).

CasePresentingHPOs: HP:0004322, HP:0007957, HP:0000924, HP:0001387 (Short stature, corneal clouding, moderate skeletal abnormalities, joint stiffness)

CaseHPOFreeText: Valgus deformity

CaseNotHPOs: N/A

CaseNotHPOFreeText: N/A

CaseEnzymeAssay: IDUA activity: 0.030 μKat/kg

CaseUrineGAGs: N/A

CaseERT: N/A

CaseBMT: N/A

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

Variant1ClinVarID: 11910

Variant1CAID: CA:236112

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

Variant2ClinVarID: 11910

Variant2CAID: CA:256112

AdditionalVariants: N/A

ParentalGenotype: N/A

PreviouslyPublished N/A

Case#: Patient 1 (see Table 1), 5 years and 6 months - deceased (age at report), 2 months (age of onset), male, height of 103 cm, weight of 13 kg, located in the Sfax: Industrial region.

DiseaseAssertion: MPS1 - severe

FamilyInfo: Two affected siblings (Patients 2 and Patient 3), three other familial relations (deceased), parents were 3rd cousins (see Table 2) aged 38 yrs (M) and 40 yrs (F).

CasePresentingHPOs: HP:0000023, HP:0000280, HP:0000365, HP:0000389 (Inguinal hernia, coarse facial feature, hearing impairment, chronic otitis)

CaseHPOFreeText: Pulmonary and cardiac deficiency

CaseNotHPOs: N/A

CaseNotHPOFreeText: N/A

CaseEnzymeAssay: N/A

CaseUrineGAGs: N/A

CaseERT: N/A

CaseBMT: N/A

Variant1: (p.F602X)

Variant1ClinVarID: N/A

Variant1CAID: N/A

Variant2: (p.F602X)

Variant2ClinVarID: N/A

Variant2CAID: N/A

AdditionalVariants: N/A

ParentalGenotype: N/A

PreviouslyPublished N/A

Case#: Patient 12 (see Table 1), 5 years old (age at report), 9 months old (age at onset), female, height of 120 cm, weight of 18 kg, located at Tunis: Industrial region

DiseaseAssertion: MPS1 - severe

FamilyInfo: Parents were 2nd cousins (see Table 2), aged 38 yrs (M) and 46 yrs (F).

CasePresentingHPOs: HP:0004322, HP:0001999, HP:0001537, HP:0007957, HP:0000924, HP:0010864 (Short stature, facial dysmorphia, umbilical hernia, corneal clouding, skeletal abnormalities, severe intellectual disability)

CaseHPOFreeText: N/A

CaseNotHPOs: N/A

CaseNotHPOFreeText: N/A

CaseEnzymeAssay: IDUA Activity - 0

CaseUrineGAGs: N/A

CaseERT: N/A

CaseBMT: N/A

Variant1: c.1743C>G (p.Y581X)

Variant1ClinVarID: 550883

Variant1CAID: CA220498

Variant2: c.1743C>G (p.Y581X)

Variant2ClinVarID: 550883

Variant2CAID: CA220498

AdditionalVariants: N/A

ParentalGenotype: N/A

PreviouslyPublished N/A

Case#: Patient 39, female, Han origin, 2 years 6 months old (age at diagnosis)

DiseaseAssertion: MPS1-H/S

FamilyInfo: N/A

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

CaseHPOFreeText: Cardiac disease

CaseNotHPOs: Global Developmental Delay (HP:0001263)

CaseNotHPOFreeText: N/A

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: 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#: Patient 5, female, Han origin, 11 years old (age at diagnosis)

DiseaseAssertion: MPS1-H/S

FamilyInfo: N/A

CasePresentingHPOs: Macrocephaly, Joint stiffness, Mongolian macula, Hepatosplenomegaly, Airway obstruction (HP:0000256, HP:0001387, HP:0011369, HP:0001433, HP:0006536)

CaseHPOFreeText: Cardiac disease

CaseNotHPOs: Global Developmental Delay, Hernia (HP:0001263, HP:0100790)

CaseNotHPOFreeText: N/A

CaseEnzymeAssay: IDUA activity 1.3 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.536C>G (p.T179R)

Variant1ClinVarID: 556358

Variant1CAID: CA355961718

Variant2: c.1898C>T (p.S633L)

Variant2ClinVarID: 556406

Variant2CAID: CA355966010

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 20, male, Han origin, 4 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: N/A

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

CaseNotHPOFreeText: Cardiac disease

CaseEnzymeAssay: IDUA activity 0.5 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.1877G>A (p.W626X)

Variant1ClinVarID: 928997

Variant1CAID: CA355965968

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 32, male, Han origin, 1 year 5 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 1.0 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.1146dupG (Paper refers to the variant as c.1147dupG, there is a typo in the article where all duplication variants are one base pair off)

Variant1ClinVarID: N/A

Variant1CAID: CA2586965958

Variant2: c.46_57del12 (p.Ser16_Ala19del)

Variant2ClinVarID: 92643

Variant2CAID: CA220509

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 45, male, Han origin, 8 years old (age at diagnosis)

DiseaseAssertion: MPS1-H/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 1.1 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.1037T>G (p.L346R)

Variant1ClinVarID: 11927

Variant1CAID: CA256128

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 by parental testing.

PreviouslyPublished N/A

Case#: Patient 11 in Group 2 (patients who were at least 3 years of age at the time of introduction of ERT), 2 years old (age of diagnosis), 3 years old (baseline age), 6 years old (current age), male, Polish

DiseaseAssertion: MPS1-S

FamilyInfo: N/A

CasePresentingHPOs: N/A

CaseHPOFreeText: Anthropometric features

CaseNotHPOs: N/A

CaseNotHPOFreeText: N/A

CaseEnzymeAssay: Diagnosis of MPS I confirmed by the biochemical determination of α-l-iduronidase deficiency in leukocytes

CaseUrineGAGs: Baseline urinary GAG values ranged from 450 to 1330 mg/g of creatinine. For treated patients the reductions of urinary GAG ranged from 30% to 80% with a mean reduction of 55%, but it never approached the normal range for age.

CaseERT: Yes - for 156 weeks he received weekly intravenous infusions of 100 U/kg (0.58 mg/kg) laronidase

CaseBMT: No

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

Variant1ClinVarID: 11909

Variant1CAID: CA204563

Variant2: c.227A>G (p.Y76C)

Variant2ClinVarID: 552686

Variant2CAID: CA2801140

AdditionalVariants: c.1345C>A (p.H449N); ClinVarID:350230, CAID:CA2802233

ParentalGenotype: N/A

PreviouslyPublished N/A

Case#: Chinese. 12 years old (age at report)

DiseaseAssertion: MPS1-H/S

FamilyInfo: N/A

CasePresentingHPOs: Short stature, macrocephaly, coarse face, corneal clouding, skeletal deformities, hepatosplenomegaly, hearing impairment, tracheal stenosis, hypertrophic cardiomyopathy, obstructive sleep apnea, umbilical hernia, anemia, ichthyosis (HP:0004322, HP:0000256, HP:0000280, HP:0007957, HP:0000924, HP:0001433, HP:0000365, HP:0002777, HP:0001639, HP:0002870, HP:0001537, HP:0001903, HP:0008064

CaseHPOFreeText: Normal intelligence, adenoid hyperplasia, tonsil hypertrophy

CaseNotHPOs: N/A

CaseNotHPOFreeText: N/A

CaseEnzymeAssay: A very low level of IDUA activity (1.8%) was detected in the patient's fibroblast cells (data not shown).

The effects of both mutations on IDUA activity and/or splicing were examined by transfection into COS-7 cells of the IDUA cDNA construct. When compared to that of wild-type cDNA, 87.5, 1.6, and 0.4% IDUA activity was observed with the IDUA cDNA containing the wild-type acceptor splice site (388-3c), the mutated acceptor splice site (388-3g), or L346R.

CaseUrineGAGs: N/A

CaseERT: N/A

CaseBMT: N/A

Variant1: c.1037T>G (p.Leu346Arg)

Variant1ClinVarID: 11927

Variant1CAID: CA256128

Variant2: c.300-3C>G; c.388-3C>G in the paper (old nomenclature)

Variant2ClinVarID: 551563

Variant2CAID: CA549265042

AdditionalVariants: p.Q33H (polymorphism)

ParentalGenotype: Maternal: c.1037T>G (p.L346R); Paternal: c.300-3C>G (c.388-3C>G in the paper, old nomenclature)

PreviouslyPublished N/A

Case#: Patient No. 1 (Table 1), White race, male, 1.97 years old (age at time of gene therapy), 75 IQ score. 2.9 years since gene therapy, 2 years since latest visit.

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.603C>G

Variant1ClinVarID: 1323100

Variant1CAID: CA355961899

Variant2: c.603C>G (p.Y603X)

Variant2ClinVarID: 1323100

Variant2CAID: CA355961899

AdditionalVariants: N/A

ParentalGenotype: N/A

PreviouslyPublished N/A

Case#: YS of sibship 7, female, 3.3 years old (age at diagnosis), 3.4 years old (age at ERT enrollment), 5.6 years (duration of ERT)

DiseaseAssertion: MPS1-HS

FamilyInfo: Affected OS (OS of sibship 7)

CasePresentingHPOs: HP:0007957, HP:0000943, HP:0002828, HP:0001263, HP:0001270 (Corneal opacity, dysostosis, joint contractures, cognitive impairment, motor impairment)

CaseHPOFreeText: Cardiac disease, somatic impairment

CaseNotHPOs: N/A

CaseNotHPOFreeText: N/A

CaseEnzymeAssay: N/A

CaseUrineGAGs: N/A

CaseERT: Yes - After 5 years of ERT, cardiac symptoms progressed but remained mild. Corneal clouding progressed as well. At the age of 5, motor development remained normal, and cognitive skills and musculoskeletal disease improved.

CaseBMT: N/A

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

Variant1ClinVarID: 11910

Variant1CAID: CA256112

Variant2: (L564fsx) No CDNA change provided.

Variant2ClinVarID: N/A

Variant2CAID: N/A

AdditionalVariants: N/A

ParentalGenotype: N/A

PreviouslyPublished N/A

Case#: OS2 of sibship 6 (see Table 1), male, 8 years old (age at diagnosis), 11 years old (age at ERT enrollment), 6 years (duration of ERT)

DiseaseAssertion: MPS1-HS

FamilyInfo: Two affected siblings (OS1 and YS 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 45–50 % of normal at T2. 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

Case#: PKMPS1P8, 10 years old (age at presentation), male, Pakastani

DiseaseAssertion: MPS-I

FamilyInfo: Born to consanguineous parents

CasePresentingHPOs: Coarse facial features, mild developmental delay, short stature, pectus carinatum, genu valgum, corneal clouding (HP:0000256, HP:0001263, HP:0004322, HP:0000768, HP:0002857, HP:0007957)

CaseHPOFreeText: Difficulty walking since the age of 4 years. Widening of the wrist, underweight, soft abdomen.

CaseNotHPOs: Visceromegaly (HP:0003271)

CaseNotHPOFreeText: N/A

CaseEnzymeAssay: N/A

CaseUrineGAGs: N/A

CaseERT: N/A

CaseBMT: N/A

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

Variant1ClinVarID:

Variant1CAID: 11919

Variant2: CA220503

Variant2ClinVarID: c.1469T>C (p.L490P)

Variant2CAID: 11919

AdditionalVariants: CA220503

ParentalGenotype: N/A

PreviouslyPublished N/A

Case#: PKMPS1P4, 16 months (age of presentation), male, Pakastani

DiseaseAssertion: MPS-I

FamilyInfo: Proband was born to a consanguineous family.

CasePresentingHPOs: Snoring, failure to thrive, developmental delay, coarse facial features, skeletal deformities, umbilical hernia (HP:0025267, HP:0001508, HP:0001263, HP:0000256, HP:0002652, HP:0001537)

CaseHPOFreeText: Copious nasal secretions, chest infections, underweight, and a liver span of 3 cm.

CaseNotHPOs: N/A

CaseNotHPOFreeText: N/A

CaseEnzymeAssay: N/A

CaseUrineGAGs: N/A

CaseERT: N/A

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#: PKMPS1P5, 10 months old (age at presentation), 2 years old (age at report), female, Pakastani

DiseaseAssertion:MPS-I

FamilyInfo: Her parents were related

CasePresentingHPOs: Upper airway obstructive symptoms, stridor, developmental delay, coarse facial features, pneumonia, umbilical hernia, short neck, kyphosis (HP:0002781, HP:0010307, HP:0001263, HP:0000256, HP:0002090, HP:0001537, HP:0000470, HP:0002808)

CaseHPOFreeText: Copious nasal discharge, widening of the wrist, liver span was 3 cm.

CaseNotHPOs: N/A

CaseNotHPOFreeText: N/A

CaseEnzymeAssay: N/A

CaseUrineGAGs: N/A

CaseERT: N/A

CaseBMT: N/A

Variant1: c.784delC (p.H262Tfs*55)

Variant1ClinVarID: 956890

Variant1CAID: CA2802083

Variant2: c.784delC (p.H262Tfs*55)

Variant2ClinVarID: 956890

Variant2CAID: CA2802083

AdditionalVariants: N/A

ParentalGenotype: N/A

PreviouslyPublished N/A

Case#: Patient II, origin of proband is Germany

DiseaseAssertion: Hurler syndrome (H)

FamilyInfo: No family information stated in this paper

CasePresentingHPOs:

CaseHPOFreeText:

CaseNotHPOs:

CaseNotHPOFreeText:

CaseEnzymeAssay: 0.01mU IDUA enzyme activity in proband. Paper states that the reference range for this proband is the control sample.

CaseUrineGAGs: Information not stated in this paper

CaseERT: Don't know

CaseBMT: Don't know

Variant1: c.979G>C, p.A327P

Variant1ClinVarID: 167190

Variant1CAID: CA234128

Variant2: Not identified in this study

Variant2ClinVarID: N/A

Variant2CAID: N/A

AdditionalVariants: No additional variants mentioned

ParentalGenotype: No parental information provided

PreviouslyPublished: I do not believe this proband was previously published. The paper states that variant "c.979G>C have been found in patients previously." It does not link the variant to a specific paper but instead references a list of papers. Here are the PMIDs of those paper: 7951228, 1301196, 1301941, and 7550232

Case#: CA-117 ID number, Table S1.1 of Supplementary Material. Male, 1 year and 4 months old (age at first symptoms), 1 year and 4 months old (age at diagnosis). Stored frozen (-20ºC) 26.5 yr

DiseaseAssertion: Severe MPS-I

FamilyInfo: N/A

CasePresentingHPOs: Kyphosis, corneal clouding, joint stiffness, learning disability (HP:0002808, HP:0007957, HP:0001387, HP:0001328)

CaseHPOFreeText: Bump on spine, thick and narrowed fingers, flat nose bridge, difficulty walking

CaseNotHPOs: N/A

CaseNotHPOFreeText: N/A

CaseEnzymeAssay: N/A

CaseUrineGAGs: 1861 fmol/punch

CaseERT: N/A

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#: CA-122 ID number, Table S1.1 of Supplementary Material. Female, 15 years old (age at first symptoms but this may be a type as the patient was diagnosed at the age of 3), 3 years old (age at diagnosis).

DiseaseAssertion: Severe MPS-I

FamilyInfo: N/A

CasePresentingHPOs: Umbilical hernia, recurrent colds, recurrent ear infections (HP:0001537, HP:0002788, HP:0410018)

CaseHPOFreeText: Joint mobility

CaseNotHPOs: N/A

CaseNotHPOFreeText: N/A

CaseEnzymeAssay: N/A

CaseUrineGAGs: 1056 fmol/punch

CaseERT: N/A

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#: CA-115 ID number, Table S1.1 of Supplementary Material. Female, 4 months old (age at first symptoms), 9 months old (age at diagnosis). Stored frozen (-20ºC) 3.4 yr

DiseaseAssertion: Severe MPS-I

FamilyInfo: N/A

CasePresentingHPOs: Hydrocephalus, hypotonia, nasal congestion (HP:0000238, HP:0001252, HP:0001742)

CaseHPOFreeText: Big head flared out, bell shaped ribs, cardiac low ejection fraction, leaky mitral value, knocked knees

CaseNotHPOs: N/A

CaseNotHPOFreeText: N/A

CaseEnzymeAssay: N/A

CaseUrineGAGs: 767 fmol/punch

CaseERT: N/A

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: 39645522

Gene: IDUA

Disease: MPS1

Inheritance: Autosomal recessive

Case#: IL-5b ID number, Table S1.1 of Supplementary Material. Additional PHI not provided.

DiseaseAssertion: Attenuated MPS-I

FamilyInfo: N/A

CasePresentingHPOs: N/A

CaseHPOFreeText: N/A

CaseNotHPOs: N/A

CaseNotHPOFreeText: N/A

CaseEnzymeAssay: N/A

CaseUrineGAGs: 1211 fmol/punch

CaseERT: N/A

CaseBMT: N/A

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

Variant1ClinVarID: 11909

Variant1CAID: CA204563

Variant2: c.793G>A (p.G265R)

Variant2ClinVarID: 638074

Variant2CAID: CA2802098

AdditionalVariants: N/A

ParentalGenotype: N/A

PreviouslyPublished N/A

Case#: CA-119 ID number, Table S1.1 of Supplementary Material. Male, at birth (age at first symptoms), 15 years and 6 months old (age at diagnosis). Stored frozen (-20ºC) 32 yr. May be the sibling of CA-120 due to closeness in ID numbers as well as having the same variants.

DiseaseAssertion: Attenuated MPS-I

FamilyInfo: N/A

CasePresentingHPOs: Premature birth, hernia (3), ear infections, joint contractures (HP:0001622, HP:0100790, HP:0410018, HP:0002828)

CaseHPOFreeText: Lung issues, hernia, spine heart (No additional information about these symptoms provided)

CaseNotHPOs: N/A

CaseNotHPOFreeText: N/A

CaseEnzymeAssay: N/A

CaseUrineGAGs: 393 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

Case#: Patient 91, Turkey

DiseaseAssertion: MPS1-H/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.1727+6T>A

Variant1ClinVarID: 2203499

Variant1CAID: CA2580070698

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

Variant2ClinVarID: 11909

Variant2CAID: CA204563

AdditionalVariants: N/A

ParentalGenotype: N/A

PreviouslyPublished N/A

Case#: Patient 93, Turkey

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.826G>A (p.E276K)

Variant1ClinVarID: 3233261

Variant1CAID: CA355962355

Variant2: c.826G>A (p.E276K)

Variant2ClinVarID: 3233261

Variant2CAID: CA355962355

AdditionalVariants: N/A

ParentalGenotype: N/A

PreviouslyPublished N/A

Case#: Patient 71, Spain

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.1190-1delG

Variant2ClinVarID: 2734639

Variant2CAID: CA2586965967

AdditionalVariants: N/A

ParentalGenotype: N/A

PreviouslyPublished N/A

Case#: Patient 99, Turkey

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.1650+5G>C

Variant1ClinVarID: N/A

Variant1CAID: CA913187450

Variant2: c.1893delC

Variant2ClinVarID: 495733

Variant2CAID: CA658683377

AdditionalVariants: N/A

ParentalGenotype: N/A

PreviouslyPublished N/A

Case#: One patient from Egypt

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.964delC in paper but correct nomenclature is c.876delC (p.Asp292GlufsTer25)

Variant1ClinVarID: 456720

Variant1CAID: CA658657370

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

Variant2ClinVarID: 11908

Variant2CAID: CA220498

AdditionalVariants: c.1360G>A (p.V454I) and c.1467C>T (p.R489=)

ParentalGenotype: N/A

PreviouslyPublished N/A

Case#: One patient from The Netherlands

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.1466G>C (p.R489P)

Variant1ClinVarID: 1518214

Variant1CAID: CA355964650

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

Variant2ClinVarID: 11908

Variant2CAID: CA220498

AdditionalVariants: N/A

ParentalGenotype: N/A

PreviouslyPublished N/A

Case#: IV-1, Female, Yemeni, deceased at age 2 years

DiseaseAssertion: Hurler Syndrome

FamilyInfo: Parents are consanguineous first cousins (Pedigree figure #1)

CasePresentingHPOs: HP:0001640, HP:0000280, HP:0002516 (Cardiomegaly, Coarse Facial Features, Intracranial hypertension)

CaseHPOFreeText: Dysplasia

CaseNotHPOs: N/A

CaseNotHPOFreeText: N/A

CaseEnzymeAssay: N/A

CaseUrineGAGs: N/A

CaseERT: N/A

CaseBMT: N/A

GenotypingMethod: Sanger Sequencing

Variant1: N/A

Variant1ClinVarID: N/A

Variant1CAID: N/A

Variant2: N/A

Variant2ClinVarID: N/A

Variant2CAID: N/A

AdditionalVariants: N/A

ParentalGenotype: Both parents are heterozygous for the c.657delA variant of the gene (see pedigree @ figure#1)

PreviouslyPublished N/A

Case#: 11, Male, 20 months (onset), 3 years (diagnosed), 9 years (report)

DiseaseAssertion: Hurler Syndrome

FamilyInfo: Not Provided

CasePresentingHPOs: HP:0000256, HP:0001387, HP:0002240, HP:0001744, HP:0001537, HP:0000407, HP:0000280, HP:0000943, HP:0007957 (Macrocephaly, Joint Stiffness, Hepatomegaly (moderate before HSCT and none at 9y), Splenomegaly (moderate before HSCT and none at 9y), Umbilical Hernia, Sensorineural hearing loss, Coarse Facial Features, Dysostosis Multiplex, Corneal Clouding)

CaseHPOFreeText: (Mental Development (Delayed since 2nd year; Developmental Quotient 73 before HSCT; mental regress after HSCT, Developmental Quotient 45 at 5y), Severe Acute graft versus host disease)

CaseNotHPOs: HP:0004322 (Short stature)

CaseNotHPOFreeText: N/A

CaseEnzymeAssay: normal IDUA activity

CaseUrineGAGs: N/A

CaseERT: N/A

CaseBMT: Hematopoietic Stem Cell Transplantation at 3y

GenotypingMethod: Not Provided

Variant1: p.Q70X

Variant1ClinVarID: 11909

Variant1CAID: CA204563

Variant2: p.Y167X

Variant2ClinVarID: N/A

Variant2CAID: CA355961650

AdditionalVariants: p.Q33H/Q33H, p.R105Q, p.N181, p.A314, p.T410, p.V454I, p.R489

ParentalGenotype: N/A

PreviouslyPublished N/A

Case#: 17, Female, 9 years (onset), 10 years (diagnosed), 10 years (report)

DiseaseAssertion: Scheie Syndrome

FamilyInfo: Patients 17 and 18 are siblings

CasePresentingHPOs: HP:0004322, HP:0002240, HP:0001537, HP:0000280, HP:0000943, HP:0007957 (Short Stature, Hepatomegaly (moderate), Umbilical Hernia, Coarse Facial Features (mild), Dysostosis Multiplex, Corneal Clouding)

CaseHPOFreeText: (Mental Development (Verbal IQ 92; Performance IQ 84; CIQ 86), Mild septal hypertrophy; mitral valve dysplasia)

CaseNotHPOs: HP:0000256, HP:0001387, HP:0001744 (Macrocephaly, Joint Stiffness, Splenomegaly)

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#: 1, Male, 4 months (onset), 2 years (diagnosed), 2 years (report), deceased

DiseaseAssertion: Hurler Syndrome

FamilyInfo: Not Provided

CasePresentingHPOs: HP:0004322, HP:0000256, HP:0001387, HP:0002240, HP:0001744, HP:0001639, HP:0001537, HP:0011947, HP:0000158, HP:0000280, HP:0000943, HP:0007957 (Short Stature, Macrocephaly, Joint Stiffness, Hepatomegaly (severe), Splenomegaly (severe), Hypertrophic Cardiomyopathy, Umbilical Hernia, Respiratory Infections, Large Tongue, Coarse Facial Features, Dysostosis Multiplex, Corneal Clouding)

CaseHPOFreeText: Mental Development (Developmental Quotient 54-62 at 2y), Systolic Murmur (3/6),

CaseNotHPOs: N/A

CaseNotHPOFreeText: N/A

CaseEnzymeAssay: N/A

CaseUrineGAGs: N/A

CaseERT: N/A

CaseBMT: N/A

GenotypingMethod: Not Provided

Variant1: p.W402X

Variant1ClinVarID: 11908

Variant1CAID: CA220498

Variant2: p.W402X

Variant2ClinVarID: 11908

Variant2CAID: CA220498

AdditionalVariants: N/A

ParentalGenotype: N/A

PreviouslyPublished N/A

Case#: 2, Male, 1 year (onset), 13 months (diagnosed), 5 years (report)

DiseaseAssertion: Hurler Syndrome

FamilyInfo: Not Provided

CasePresentingHPOs: HP:0001387, HP:0002240, HP:0001744, HP:0001537, HP:0000023, HP:0000365, HP:0000158, HP:0000280, HP:0000943, HP:0007957 (Joint Stiffness, Hepatomegaly (moderate before HSCT, mild after HSCT), Splenomegaly (mild), Umbilical Hernia, Inguinal Hernia, Deafness, Large Tongue, Coarse Facial Features, Dysostosis Multiplex, Corneal Clouding)

CaseHPOFreeText: Mental Development (Normal development till 1y, developmental quotient 79 at 2y), Systolic Murmur (1/6; Ejection fraction of 68% at 4 years old)

CaseNotHPOs: HP:0004322, HP:0000256 (Short Stature, Macrocephaly)

CaseNotHPOFreeText: N/A

CaseEnzymeAssay: N/A

CaseUrineGAGs: N/A

CaseERT: N/A

CaseBMT: Hematopoietic Stem Cell Transplantation in 2 years (chimerism)

GenotypingMethod: Not Provided

Variant1: p.W402X

Variant1ClinVarID: 11908

Variant1CAID: CA220498

Variant2: p.W402X

Variant2ClinVarID: 11908

Variant2CAID: CA220498

AdditionalVariants: N/A

ParentalGenotype: N/A

PreviouslyPublished N/A

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.1882C>T (p.R628X)

Variant2ClinVarID: 550421

Variant2CAID: CA2802462

AdditionalVariants: N/A

ParentalGenotype: N/A

PreviouslyPublished N/A

Case#: Patient 6, Turkish

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.793-5C>A (homozygous)

Variant1ClinVarID: N/A

Variant1CAID: CA3250086379

Variant2: c.793-6C>G (homozygous)

Variant2ClinVarID: N/A

Variant2CAID: CA2739858898

AdditionalVariants: N/A

ParentalGenotype: N/A

PreviouslyPublished N/A

PMID: 31298590

Gene: IDUA

Disease: MPS1

Inheritance: Autosomal recessive

PMID: 31298590

Gene: IDUA

Disease: MPS1

Inheritance: Autosomal recessive

Case#: Patient 41 (Table 3)

DiseaseAssertion: Moderate MPS 1

FamilyInfo: N/A

CasePresentingHPOs: N/A

CaseHPOFreeText: N/A

CaseNotHPOs: N/A

CaseNotHPOFreeText: N/A

CaseEnzymeAssay: 77.5 DBS protein concentration determined by Immuno-SRM (pmol/L).

CaseUrineGAGs: N/A

CaseERT: Yes

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#: MPS I_Case 04, male newborn

DiseaseAssertion: MPS type I, MPS I, MPS-I, attenuated MPS I

FamilyInfo: No family information provided

CasePresentingHPOs:

CaseHPOFreeText:

CaseNotHPOs:

CaseNotHPOFreeText: This proband is believed to be an affected MPS-patient however, the proband did not have any obvious clinical symptoms to date (up to two years of age). The paper states that this attenuated MPS I case will need a long term follow up.

CaseEnzymeAssay: Proband identified by newborn screening. alpha-L-iduronidase activity in dried blood spot sample is 0.54 umole/L/Hr; this is below the study's DBS enzyme activity cutoff value of 3 umol/L/h

CaseUrineGAGs: Urine DMB GAG ratio, dermatan sulfate amount, heparan sulfate amount, and keratan sulfate amount was not calculated for this proband because their parents refused further analysis

CaseERT: Don't know (would assume no since the proband is a newborn)

CaseBMT: Don't know (would assume no since the proband is a newborn)

Variant1: c.1079T>G, p.F360C

Variant1ClinVarID:

Variant1CAID: CA355963276

Variant2: c.1359_1384del, p.S453Rfs*47

Variant2ClinVarID:

Variant2CAID: CA3051384105

AdditionalVariants: No additional variants mentioned

ParentalGenotype: No parental testing results are available

PreviouslyPublished No statement from the author indicating the proband is previously published. Since this is a newborn study, I strongly believe this is the proband’s first time being published.

Case#: MPS I_Case 03, female newborn

DiseaseAssertion: MPS type I, MPS I, MPS-I, attenuated MPS I

FamilyInfo: MPS I_Case 03 and MPS I_Case 02 are twins

CasePresentingHPOs:

CaseHPOFreeText:

CaseNotHPOs:

CaseNotHPOFreeText: This proband is believed to be an affected MPS-patient however, the proband did not have any obvious clinical symptoms to date (up to two years of age). The paper states that this attenuated MPS I case will need a long term follow up.

CaseEnzymeAssay: Proband identified by newborn screening. alpha-L-iduronidase activity in dried blood spot sample is 0.51 umole/L/Hr; this is below the study's DBS enzyme activity cutoff value of 3 umol/L/h

CaseUrineGAGs: Urine DMB GAG ratio is 239.3 mg/mmol creatinine. 41.04 ug/ml dermatan sulfate in urine (<0.41 ug/ml is the reference cutoff for dermatan sulfate in this study). 2.93 ug/ml ug/ml heparan sulfate in urine (<0.8 ug/ml is the reference cutoff for heparan sulfate in this study). 0.00 ug/ml keratan sulfate in urine.

CaseERT: Don't know (would assume no since the proband is a newborn)

CaseBMT: Don't know (would assume no since the proband is a newborn)

Variant1: c.1037T>G, p.L346R

Variant1ClinVarID: 11927

Variant1CAID: CA256128

Variant2: c.1091C>T, p.T364M

Variant2ClinVarID: 11925

Variant2CAID: CA256126

AdditionalVariants: No additional variants mentioned

ParentalGenotype: No parental testing results are available

PreviouslyPublished No statement from the author indicating the proband is previously published. Since this is a newborn study, I strongly believe this is the proband’s first time being published.

Case#: Patient 13, born in 2010 (paper published in 2017), 16 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: 55 ng/mol (36 weight matched enzyme reference assay)

CaseUrineGAGs: 0.28 DS/CS

CaseERT: N/A

CaseBMT: Yes, MUD (GOS)

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: 24102521

Gene: IDUA

Disease: MPS1

Inheritance: Autosomal recessive

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: H82P

Variant1ClinVarID: 195039

Variant1CAID: CA201510

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: E178K

Variant1ClinVarID: 2203495

Variant1CAID: CA355961709

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: P385R

Variant1ClinVarID: 556024

Variant1CAID: CA355963438

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: H240R

Variant1ClinVarID: 947028

Variant1CAID: CA355962127

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:

Variant1ClinVarID:

Variant1CAID: CA355963739

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: D315Y

Variant1ClinVarID:

Variant1CAID: CA355962740

Variant2: N/A

Variant2ClinVarID: N/A

Variant2CAID: N/A

AdditionalVariants: N/A

ParentalGenotype: N/A

PreviouslyPublished: N/A

Case#: Family 15, Guernsey

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.208C>T (p.Q70X)

Variant1ClinVarID: 11909

Variant1CAID: CA204563

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

Variant2ClinVarID: 280976

Variant2CAID: CA2802455

AdditionalVariants: N/A

ParentalGenotype: N/A

PreviouslyPublished N/A

Case#: Family 22, Pakistan

DiseaseAssertion: MPS1-H/S

FamilyInfo: N/A

CasePresentingHPOs: N/A

CaseHPOFreeText: N/A

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.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

PMID: 23210910

Gene: IDUA

Disease: MPS1

Inheritance: Autosomal recessive

Case#: Patient 24, female, 15 months (age at presentation).

DiseaseAssertion: MPS1-H

FamilyInfo: Consanguinity in the family present for this patient.

CasePresentingHPOs: Coarse facial features, global developmental delay, joint contractures (HP:0000256, HP:0001263, HP:0100790)

CaseHPOFreeText: N/A

CaseNotHPOs: N/A

CaseNotHPOFreeText: N/A

CaseEnzymeAssay: N/A

CaseUrineGAGs: N/A

CaseERT: N/A

CaseBMT: N/A

Variant1: c.1759C>T (p.Q587X)

Variant1ClinVarID: 2630132

Variant1CAID: CA355965402

Variant2: c.1759C>T (p.Q587X)

Variant2ClinVarID: 2630132

Variant2CAID: CA355965402

AdditionalVariants: N/A

ParentalGenotype: N/A

PreviouslyPublished N/A

Case#: Patient 8, female, 5 months (age at presentation).

DiseaseAssertion: MPS1-H

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

CasePresentingHPOs: Corneal clouding, coarse facial features, dysostosis multiplex, global developmental delay, hepatomegaly, joint stiffness, splenomegaly (HP:0007957, HP:0000256, HP:0000943, HP:0001263, HP:0002240, HP:0001387, 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.362T>C (p.L121P)

Variant1ClinVarID: 1343382

Variant1CAID: CA355961174

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

Variant2ClinVarID: 1343382

Variant2CAID: CA355961174

AdditionalVariants: N/A

ParentalGenotype: Mother and father are both carriers

PreviouslyPublished N/A

Case#: Patient 17, male, 4 years (age at presentation).

DiseaseAssertion: MPS1-H

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

CasePresentingHPOs: Corneal clouding, coarse facial features, dystosis multiplex, global developmental delay, hepatomegaly, joint stiffness, splenomegaly, recurrent respiratory infection, 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.1115A>G (p.N372S)

Variant1ClinVarID: 554765

Variant1CAID: CA355963365

Variant2: c.1160T>C (p.L387P)

Variant2ClinVarID: 556106

Variant2CAID: CA355963451

AdditionalVariants: N/A

ParentalGenotype: N/A

PreviouslyPublished N/A

Case#: Patient 1, female, 2 years (age at presentation)

DiseaseAssertion: MPS1-H

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

CasePresentingHPOs: Corneal clouding, coarse facial features, dysostosis multiplex, intellectual disability (HP:0007957, HP:0000256, HP:0000943, HP:0010864)

CaseHPOFreeText: N/A

CaseNotHPOs: N/A

CaseNotHPOFreeText: N/A

CaseEnzymeAssay: N/A

CaseUrineGAGs: N/A

CaseERT: N/A

CaseBMT: N/A

Variant1: c.1A>G (p.M1?)

Variant1ClinVarID: 1323098

Variant1CAID: CA355945206

Variant2: c.1A>G (p.1M?)

Variant2ClinVarID: 1323098

Variant2CAID: CA355945206

AdditionalVariants: N/A

ParentalGenotype: N/A

PreviouslyPublished N/A

Case#: Pt 6, age is 18 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.W402X

Variant1ClinVarID:

Variant1CAID: PA3051368272

Variant2: c.1163delC

Variant2ClinVarID: 828094

Variant2CAID: CA915942984

AdditionalVariants: No additional variants mentioned

ParentalGenotype: No parental information provided

PreviouslyPublished: No mention of being previously published

Case#: Pt 2, 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.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#: Patient 2, female, German, 1.5yo at HSCT, 3.5yo at report

DiseaseAssertion: MPS I, Hurler

FamilyInfo: n/a

CasePresentingHPOs:

CaseHPOFreeText: diagnosis of MPS I confirmed by enzyme activity determination and/or genetic testing, Hurler phenotype, hematopoietic stem cell transplantation (HSCT) and a minimum of two orthopedic evaluations. enzyme replacement therapy (ERT) prior to HSCT. severely limited shoulder abduction (deficit ≥90°), mild flexion joint contractures of elbows, hips and knees (5–15°). normal odontoid process and increased soft tissue mass surrounding the odontoid. Flattened and beaked vertebrae and paddle shaped ribs.

CaseNotHPOs:

CaseNotHPOFreeText: thoracolumbar kyphosis was absent at an average age of 1.6 years

GenotypingMethod: n/a

PreviouslyPublished: n/a

Variant: c.606C > A p.Y202X; c.979G > C p.A327P

CAID: CA355961907

SupplementalData: n/a

Case#: Patient 11 (see Table 2), male, 19 years old (age at report), 9.4 years (duration of treatment), 8 surgeries

DiseaseAssertion: MPS1-HS

FamilyInfo: N/A

CasePresentingHPOs: HP:0000238, HP:0002176 (Hydrocephalus, Spinal cord compression)

CaseHPOFreeText:

CaseNotHPOs: HP:0002360 (sleep abnormality)

CaseNotHPOFreeText: Shunt placement, psychiatric problems

CaseEnzymeAssay: N/A

CaseUrineGAGs: N/A

CaseERT: Yes

CaseBMT: N/A

Variant1: c.265C>T (p.R89W)

Variant1ClinVarID: 580286

Variant1CAID: CA2801156

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

Variant2ClinVarID: 11908

Variant2CAID: CA220498

AdditionalVariants: N/A

ParentalGenotype: N/A

PreviouslyPublished N/A

Case#: Patient 9 (see Table 2), male, 12.7 years old (age at report), 7 years (duration of treatment), 7 surgeries

DiseaseAssertion: MPS1-HS

FamilyInfo: N/A

CasePresentingHPOs:

CaseHPOFreeText:

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.1139A>G (p.Q380R)

Variant1ClinVarID: 550799

Variant1CAID: CA2802202

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

Variant2ClinVarID: 11909

Variant2CAID: CA204563

AdditionalVariants: N/A

ParentalGenotype: N/A

PreviouslyPublished N/A

PMID: 28844463

Gene: IDUA

Disease: MPS1

Inheritance: Autosomal recessive

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.1504C>T (p.R502W)

Variant1ClinVarID: 2070831

Variant1CAID: CA2802280

Variant2: c.1504C>T (p.R502W)

Variant2ClinVarID: 2070831

Variant2CAID: CA2802280

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.1163C>T (p.T388M)

Variant1ClinVarID: 558615

Variant1CAID: CA355963455

Variant2: c.1163C>T (p.T388M)

Variant2ClinVarID: 558615

Variant2CAID: CA355963455

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.1855C>T (p.R619X)

Variant1ClinVarID: 280976

Variant1CAID: CA2802455

Variant2: c.1169T>C (p.M390T)

Variant2ClinVarID: 1496867

Variant2CAID: CA355963466

AdditionalVariants: N/A

ParentalGenotype: N/A

PreviouslyPublished N/A

Case#: Patient 5, female, 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: 0.7 nmol/mg/h (reference range 135 ± 57 nmol/mg/h)

CaseUrineGAGs: 27.57 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.1139A>G (p.Q380R)

Variant2ClinVarID: 550779

Variant2CAID: CA2802202

AdditionalVariants: N/A

ParentalGenotype: N/A

PreviouslyPublished N/A

Case#: No additional case information provided

DiseaseAssertion: MPSI-H

FamilyInfo: N/A

CasePresentingHPOs: N/A

CaseHPOFreeText: N/A

CaseNotHPOs: N/A

CaseNotHPOFreeText: N/A

CaseEnzymeAssay: 0.05 umol/g hr, reference range 10–50 umol/g hr.

CaseUrineGAGs: N/A

CaseERT: N/A

CaseBMT: N/A

Variant1: c.36_44delGCTCCTGGC (p.Leu13_Ala15del)

Variant1ClinVarID: 3720558

Variant1CAID: CA645372295

Variant2: c.1205G>A (W402X)

Variant2ClinVarID: 11908

Variant2CAID: CA220498

AdditionalVariants: N/A

ParentalGenotype: N/A

PreviouslyPublished N/A

Case#: 5, Female, 1.2 years (diagnosed), 10.5 years (report), 10.5 kg (weight), 87 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, Cardiac Manifestations (Mitral stenosis/ Aortic insufficiency)

CaseNotHPOs: HP:0007957 (Corneal Opacity)

CaseNotHPOFreeText: N/A

CaseEnzymeAssay: IDUA activity 1.69 (μmol/spot.20h)

CaseUrineGAGs: Quantitative urinary GAG 14.80 (mg/gCr)

CaseERT: N/A

CaseBMT: N/A

GenotypingMethod: Sanger Sequencing

Variant1: p.D257G

Variant2: N/A

AdditionalVariants: N/A

ParentalGenotype: N/A

PreviouslyPublished: N/A

Case#: Patient 3, Male, 2 years (diagnosed), 12 years (report), Sfax (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

Case#: Boy 1, male, 10 years old, born at full-term with a birth weight of 3,400 grams.

DiseaseAssertion: MPS-I H/S

FamilyInfo: Boy 1 was born to a Chinese family of five members, with a total of 3 boys. Genetic testing was conducted on all 5 family members. The first and third child (boy 1 and boy 3) have MPS I. The second son had a normal phenotype and genotype.

CasePresentingHPOs: Claw hands, limitation of joint mobility, corneal clouding (HP:0034337, HP:0001376, HP:0007957)

CaseHPOFreeText: Swollen knee, lesions (noted at 3 years old)

CaseNotHPOs: N/A

CaseNotHPOFreeText: N/A

CaseEnzymeAssay: 3.84 nmol/h/mg (reference range >21)

CaseUrineGAGs: Positive for urinary polysaccharide toluidine blue staining test

CaseERT: N/A

CaseBMT: N/A

Variant1: c.265C>T (p.R89W)

Variant1ClinVarID: 580286

Variant1CAID: CA2801156

Variant2: c.1633G>T (p.E545X)

Variant2ClinVarID: N/A

Variant2CAID: CA355965099

AdditionalVariants: N/A

ParentalGenotype: Mother carries c.265C>T and father carries c.1633G>T.

PreviouslyPublished N/A

Case#: P2, male, 1.8 years (age at HCT - hematopoietic cell transplantation), 14 iPS colonies per 100,000 cells (KC), 4 iPS colonies per 100,000 cells (MSC).

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, and MSC, mesenchymal stromal cells.

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#: Pt4, Male, 9 months (diagnosis), 9 months (onset)

DiseaseAssertion: Hurler Syndrome

FamilyInfo: N/A Pedigree (Figure 4Pt4)

CasePresentingHPOs: HP:0000280, HP:0000365, HP:0100814, (Coarse face, Hearing Loss, Dermal melanocytosis)

CaseHPOFreeText: Spinal Deformation, Inguinal or Umbilical hernia

CaseNotHPOs: HP:0007957, HP:0001387, HP:0001654, HP:0001433, (Cornea clouding, Joint stiffness, Valvular heart disease, Hepatosplenomegaly)

CaseNotHPOFreeText: Long bone deformation

CaseEnzymeAssay: α-L-iduronidase 0.01 (leukocytes, normal 15.9–41.8 nmol/mg prot/h)

CaseUrineGAGs: Urine glycosaminoglycans 1106.4 (mg/g creatinine) {10.7-112}

CaseERT: N/A

CaseBMT: N/A

GenotypingMethod: Not Provided.

Variant1: c.1862G>C

Variant1ClinVarID: 1038439

Variant1CAID: CA355965939

Variant2: c.1862G>C

Variant2ClinVarID: 1038439

Variant2CAID: CA355965939

AdditionalVariants: N/A

ParentalGenotype: Both parents are heterozygous for c.1862G>C variant (figure 4 Pt 4)

PreviouslyPublished: N/A