Case#: YS2 of sibship 5 (see Table 1), female, 0.1 years old (age at diagnosis), 2.5 years old (age at ERT enrollment), 8.8 years (duration of ERT)

DiseaseAssertion: MPS1-HS

FamilyInfo: Two affected siblings (OS and YS1 of sibship 5)

CasePresentingHPOs: HP:0007957, HP:0002828, HP:0001270 (Corneal opacity, joint contractures, motor delay)

CaseHPOFreeText: Cardiac disease, ocular disease, organomegaly

CaseNotHPOs: HP:0000943 (Dysostosis)

CaseNotHPOFreeText: N/A

CaseEnzymeAssay: N/A

CaseUrineGAGs: N/A

CaseERT: Yes - Organomegaly and motor function delays improved, cardiac symptoms remained stable, and mild joint contractures developed. 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#: 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#: OS of sibship 5 (see Table 1), female, 3 years old (age at diagnosis), 5.8 years old (age at ERT enrollment), 8.6 years (duration of ERT)

DiseaseAssertion: MPS1-HS

FamilyInfo: Two affected YS (YS1 and YS2 of sibship 5)

CasePresentingHPOs: HP:0007957, HP:0002828, HP:0001270 (Corneal opacity, joint contractures, motor delay)

CaseHPOFreeText: Cardiac disease, ocular disease

CaseNotHPOs: HP:0000943 (Dysostosis)

CaseNotHPOFreeText: N/A

CaseEnzymeAssay: N/A

CaseUrineGAGs: N/A

CaseERT: Yes - There were improvements in organomegaly and motor function. Pulmonary function was at 30–40 % of normal at follow-up (no information available at T1). Ocular involvement and lower extremity joint symptoms progressed, but cardiac disease remained stable.

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#: Patient 22, female, 4 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 stiffness, sleep disturbance, splenomegaly (HP:0007957, HP:0000256, HP:0000943, HP:0002240, HP:0001387, HP:0002360, 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.1469T>C (p.L490P)

Variant1ClinVarID: 11919

Variant1CAID: CA220503

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

Variant2ClinVarID: 556406

Variant2CAID: CA355966010

AdditionalVariants: N/A

ParentalGenotype: N/A

PreviouslyPublished N/A

Case#: Patient 21, male, 4 years (age at presentation).

DiseaseAssertion: MPS1-H/S

FamilyInfo: Consanguinity in the family present for this patient.

CasePresentingHPOs: Corneal clouding, coarse facial features, dystosis multiplex, hepatomegaly, joint stiffness, motor delay, splenomegaly (HP:0007957, HP:0000256, HP:0000943, HP:0002240, HP:0001387, HP:0001270, 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.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#: Patient 20, male, 8 years (age at presentation).

DiseaseAssertion: MPS1-H/S

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

CasePresentingHPOs: Corneal clouding, coarse facial features, cardiomyopathy, dystosis multiplex (HP:0007957, HP:0000256, HP:0001638, HP:0000943)

CaseHPOFreeText: N/A

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#: PKMPS1P12, 2.6 years old (age at presentation), male, Pakastani

DiseaseAssertion: MPS-I

FamilyInfo: Born to a non-consanguineous couple

CasePresentingHPOs: Significant developmental delay, stridor, coarse facial features, recurrent chest infections, umbilical hernia, corneal clouding (HP:0001263, HP:0010307, HP:0000256, HP:0002783, HP:0001537, HP:0007957)

CaseHPOFreeText: Running nose, skeletal stigmata were consistent with MPS1, and a liver span on 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#: PKMPS1P11, 8 years old (age at presentation), female, Pakastani. Poor performance in school due to difficulty in writing.

DiseaseAssertion: MPS-I

FamilyInfo: Born to parents in a consanguineous marriage

CasePresentingHPOs: Coarse facial features, joint stiffness, stunted and mild thoracic kyphosis (HP:0000256, HP:0001387, HP:0002808)

CaseHPOFreeText: Widening of the wrist

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#: PKMPS1P6, 8 months old (age at presentation), 2 years old (age at report), female, Pakastani

DiseaseAssertion: MPS-I

FamilyInfo: Proband's parents were first cousins.

CasePresentingHPOs: Coarse facial features, recurrent respiratory tract infections, joint stiffness, upper airway obstructive symptoms, mild developmental delay, umbilical hernia (HP:0000256, HP:0002788, HP:0001387, HP:0002781, HP:0001263, HP:0001537)

CaseHPOFreeText: Widening of the wrist and a stunted, pectus carinatum

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: 11919

Variant1CAID: CA220503

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

Variant2ClinVarID: 11919

Variant2CAID: CA220503

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#: 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: L490P

Variant1ClinVarID: 11919

Variant1CAID: CA220503

Variant2: N/A

Variant2ClinVarID: N/A

Variant2CAID: N/A

AdditionalVariants: N/A

ParentalGenotype: N/A

PreviouslyPublished: N/A

Case#: Patient 62, 2 years old (age at report), female, Indian

DiseaseAssertion: MPS1-H

FamilyInfo: N/A

CasePresentingHPOs: Dysostosis multiplex (HP:0000943)

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.1240delA (p.Ser414Alafs*26)

Variant1ClinVarID: 4086094

Variant1CAID: CA645372298

Variant2: c.1469T>C (p.Leu490Pro)

Variant2ClinVarID: 11919

Variant2CAID: CA220503

AdditionalVariants: N/A

ParentalGenotype: N/A

PreviouslyPublished N/A

Case#: Patient 54, 8 years old (age at report), female, Indian

DiseaseAssertion: MPS1-H

FamilyInfo: N/A

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

CaseHPOFreeText: N/A

CaseNotHPOs: N/A

CaseNotHPOFreeText: N/A

CaseEnzymeAssay: 2.3% (Range of residual enzyme activity: 0.0%-4.8%)

CaseUrineGAGs: N/A

CaseERT: N/A

CaseBMT: N/A

Variant1: c.568_581del (p.Asn190His)

Variant1ClinVarID: 3639714

Variant1CAID: CA2801994

Variant2: c.1469T>C (p.Leu490Pro)

Variant2ClinVarID: 11919

Variant2CAID: CA220503

AdditionalVariants: N/A

ParentalGenotype: N/A

PreviouslyPublished N/A

Case#: Patient IV, origin of proband is Pakistani/Norway, male (hinted that proband is male in figure 1 caption)

DiseaseAssertion: Hurler syndrome (H)

FamilyInfo: No family information provided, but genotype information is provided (see ParentalGenotype)

CasePresentingHPOs:

CaseHPOFreeText:

CaseNotHPOs:

CaseNotHPOFreeText:

CaseEnzymeAssay: 0.00 umol/mghour IDUA enzyme activity in patient IV. Reference range is 0.14 - 0.35 umol/mghour

CaseUrineGAGs: Information not stated in this paper

CaseERT: Don't know

CaseBMT: Don't know

Variant1: c.1469T>C, p.L490P

Variant1ClinVarID: 11919

Variant1CAID: CA220503

Variant2: c.(1828 + 1_1829‐1)(*1963?)del

Variant2ClinVarID: Not sure how to look up in CAR

Variant2CAID: Not sure how to look up in CAR

AdditionalVariants: No additional variants mentioned.

ParentalGenotype: Figure 1 has parental genotype information for this proband. It is stated that there is a "hereozygous presence" of an IDUA variant in DNA of patient IV's mother. It is suggested that patient IV inherited a pathogenic variant from his mother. The father of patient IV "carries a benign single nucleotide variant rs115929690 suggesting that patient IV has inherited... a benign variant from his father"

PreviouslyPublished: I do not believe this proband was previously published. The paper states that variant "c.1469T>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#: Case information was not provided

DiseaseAssertion: MPS I-H/S

FamilyInfo: Proband of family B

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.1469T>C (p.L490P)

Variant1ClinVarID: 11919

Variant1CAID: CA220503

Variant2: c.1469T>C (p.L490P), Confirmed homozygous in Figure 1

Variant2ClinVarID: 11919

Variant2CAID: CA220503

AdditionalVariants: N/A

ParentalGenotype: N/A

PreviouslyPublished N/A

Case#: Functional assay variant with a clinical significance of 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.1469T>C (p.L490P)

Variant1ClinVarID: 11919

Variant1CAID: CA220503

Variant2: N/A

Variant2ClinVarID: N/A

Variant2CAID: N/A

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

Case#: Family 21, 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

Case#: 0.3% residual activity at 37 °C

DiseaseAssertion: MPS1-H/S

FamilyInfo: N/A

CasePresentingHPOs: N/A

CaseHPOFreeText: N/A

CaseNotHPOs: N/A

CaseNotHPOFreeText: N/A

CaseEnzymeAssay: 0.9 ± 0.1 nmol/mg/h IDUA activity at 37 °C

CaseUrineGAGs: N/A

CaseERT: N/A

CaseBMT: N/A

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

Variant1ClinVarID: 11919

Variant1CAID: CA220503

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

ClinVarID: 11919

Variant2CAID: CA220503

AdditionalVariants: N/A

ParentalGenotype: N/A

PreviouslyPublished N/A

Case#: Patient 82, 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.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