PMID: 31400021 Gene: IDUA Disease: MPS1 Inheritance: Autosomal recessive

PMID: 36951468

Gene: IDUA

Disease: MPS1

Inheritance: Autosomal recessive

PMID: 30737479

Gene: IDUA

Disease: MPS1

Inheritance: Autosomal recessive

Case#: Infant #12, male.

DiseaseAssertion: MPS-I

FamilyInfo: N/A

CasePresentingHPOs: N/A

CaseHPOFreeText: N/A

CaseNotHPOs: N/A

CaseNotHPOFreeText: N/A

CaseEnzymeAssay: 0.95 IDUA enzyme activity (Ref. 5.9–27.8 μmol/g protein/h)

CaseUrineGAGs: DMB/Cre. Ratio - 18.53, DS - 0.09, HS - 0.17, KS - 0.78 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.1093C>G (p.L365V)

Variant1ClinVarID: 728422

Variant1CAID: CA2802186

Variant2: c.1463G>C (p.R488P)

Variant2ClinVarID: N/A

Variant2CAID: CA355964644

AdditionalVariants: c.1828+5G>A, ClinVarID: 928996, CAID: CA2802421

ParentalGenotype: N/A

PreviouslyPublished N/A

Case#: Infant #9, female.

DiseaseAssertion: MPS-I

FamilyInfo: N/A

CasePresentingHPOs: N/A

CaseHPOFreeText: N/A

CaseNotHPOs: N/A

CaseNotHPOFreeText: N/A

CaseEnzymeAssay: 0.46 IDUA enzyme activity (Ref. 5.9–27.8 μmol/g protein/h)

CaseUrineGAGs: DMB/Cre. Ratio - 33.61, DS - 5.91, HS - 9.38, KS - 0.28 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.300-3C>G

Variant1ClinVarID: 551563

Variant1CAID: CA549265042

Variant2: c.1874A>C (p.Y625S)

Variant2ClinVarID: 2910181

Variant2CAID: CA355965961

AdditionalVariants: N/A

ParentalGenotype: N/A

PreviouslyPublished N/A

Case#: Infant #7, female.

DiseaseAssertion: MPS-I

FamilyInfo: N/A

CasePresentingHPOs: N/A

CaseHPOFreeText: N/A

CaseNotHPOs: N/A

CaseNotHPOFreeText: N/A

CaseEnzymeAssay: 21.60 IDUA enzyme activity (Ref. 5.9–27.8 μmol/g protein/h)

CaseUrineGAGs: DMB/Cre. Ratio - 26.82, DS - 0.20, HS - 0.01, KS - 6.49 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.76G>A (p.A26T)

Variant1ClinVarID: 712785

Variant1CAID: CA280110

Variant2: c.911delT (p.V304Gfs*13)

Variant2ClinVarID: 1184991

Variant2CAID: CA2573052265

AdditionalVariants: N/A

ParentalGenotype: N/A

PreviouslyPublished N/A

Case#: Patient 12 in Group 2 (patients who were at least 3 years of age at the time of introduction of ERT), 5 years old (age of diagnosis), 15 years old (baseline age), 19 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 208 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.793G>C (p.G265R)

Variant2ClinVarID: 638074

Variant2CAID: CA2802098

AdditionalVariants: N/A

ParentalGenotype: N/A

PreviouslyPublished N/A

PMID: 19783188

Gene: IDUA

Disease: MPS1

Inheritance: Autosomal recessive

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#: OS of sibship 7, female, 4.3 years old (age at diagnosis), 4.5 years old (age at ERT enrollment), 5.5 years (duration of ERT)

DiseaseAssertion: MPS1-HS

FamilyInfo: Affected YS (YS 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 stabilized, and musculoskeletal symptoms, motor development, and corneal clouding progressed.

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#: Patient 1, 9 years old, Iranian

DiseaseAssertion: MPSI-H (Severe)

FamilyInfo: N/A

CasePresentingHPOs: N/A

CaseHPOFreeText: N/A

CaseNotHPOs: N/A

CaseNotHPOFreeText: N/A

CaseEnzymeAssay: 0.12 µmol/g.h (Normal ranges: 10-50 µmol/g.h)

CaseUrineGAGs: N/A

CaseERT: N/A

CaseBMT: N/A

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

Variant1ClinVarID: N/A

Variant1CAID: CA355961573

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

Variant2ClinVarID: N/A

Variant2CAID: CA355961573

AdditionalVariants: N/A

ParentalGenotype: N/A

PreviouslyPublished N/A

PMID: 22074387

Gene: IDUA

Disease: MPS1

Inheritance: Autosomal recessive

Case#: Family E proband, female, 18 months old (age of diagnosis), 11 years old (age of death), Tunisia.

DiseaseAssertion: MPS1-H

FamilyInfo: No affected family members (See Fig. 1), parents were 1st degree relatives (See Table 1). The family benefited from a prenatal diagnosis showing a normal enzymatic activity (3.5 nmol/h/mg) (usual values: 1-5).

CasePresentingHPOs: HP:0001999, HP:0030799, HP:0002652, HP:0000687, HP:0030812, HP:0012471, HP:0000574, HP:0001537, HP:0001653, HP:0002673, HP:0001433, HP:0001640, HP:0004322 (Abnormal facial shape, scaphocephaly, skeletal dysplasia, widely spaced teeth, enlarged tonsils, thick lips, bushy eyebrows, umbilical hernia, mitral valve regurgitation, coax valga, hepatosplenomegaly, cardiomegaly, short stature

CaseHPOFreeText: Compression of the medulla

CaseNotHPOs: N/A

CaseNotHPOFreeText: N/A

CaseEnzymeAssay: IDUA activity (0.5 nmol/h/mg) (usual values: 1-5 nmol/h/mg).

CaseUrineGAGs: glycosaminoglycans (125 mg/g of creatinine) (usual values: 9-46), abnormal electrophoresis profile with dermatan sulfate and heparan sulfate.

CaseERT: N/A

CaseBMT: N/A

Variant1: c.530T>C (p.F177S)

Variant1ClinVarID: N/A

Variant1CAID: CA355961706

Variant2: c.530T>C (p.F177S)

Variant2ClinVarID: N/A

Variant2CAID: CA355961706

AdditionalVariants: N/A

ParentalGenotype: N/A

PreviouslyPublished N/A

Case#: No additional case information provided

DiseaseAssertion: N/A

FamilyInfo: N/A

CasePresentingHPOs: N/A

CaseHPOFreeText: N/A

CaseNotHPOs: N/A

CaseNotHPOFreeText: N/A

CaseEnzymeAssay: 0.09 umol/g hr, reference range 10–50 umol/g hr.

CaseUrineGAGs: N/A

CaseERT: N/A

CaseBMT: N/A

Variant1: c.1187T>G (p.L396R)

Variant1ClinVarID: N/A

Variant1CAID: CA355963497

Variant2: c.1187T>G (p.L396R)

Variant2ClinVarID: N/A

Variant2CAID: CA355963497

AdditionalVariants: N/A

ParentalGenotype: N/A

PreviouslyPublished N/A

1 individual was reported to have this variant from the cohort UK cohort of 145 people.

Genotype: NM_000203.3 c.1205G>A p.(Trp402Ter) c.1728-1G>C

HPOFreeText: Phenotype: Sev: 1 (H) "classification of a “severe” phenotype was based on the presence of one or more of the following: presentation with clinical features of MPS I and diagnosis before 12 months of age; significant developmental delay in a child with clinical features of MPS I under 30 months of age; sibling of a child with MPS I also classified as “severe phenotype.”"

GenotypingMethod: bidirectional Sanger sequencing of the IDUA gene. IDUA exons and adjacent intron regions were amplified by PCR reactions and then sequenced

Case#: Patient 8, 3 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: 3.1% (Range of residual enzyme activity: 0.0%-4.8%)

CaseUrineGAGs: N/A

CaseERT: N/A

CaseBMT: N/A

Variant1: c.436A>T (p.Lys146Ter)

Variant1ClinVarID: N/A

Variant1CAID: CA355961453

Variant2: c.436A>T (p.Lys146Ter)

Variant2ClinVarID: N/A

Variant2CAID: CA355961453

AdditionalVariants: N/A

ParentalGenotype: N/A

PreviouslyPublished N/A

Case#: Patient 27, 4 months old (age at report), female, Indian

DiseaseAssertion: MPS1-H

FamilyInfo: N/A

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

CaseHPOFreeText: N/A

CaseNotHPOs: N/A

CaseNotHPOFreeText: N/A

CaseEnzymeAssay: 3.7% (Range of residual enzyme activity: 0.0%-4.8%)

CaseUrineGAGs: N/A

CaseERT: N/A

CaseBMT: N/A

Variant1: c.1249_1275del (p.Thr417_His425del)

Variant1ClinVarID: 556156

Variant1CAID: CA658823291

Variant2: c.1249_1275del (p.Thr417_His425del)

Variant2ClinVarID: 556156

Variant2CAID: CA658823291

AdditionalVariants: N/A

ParentalGenotype: N/A

PreviouslyPublished N/A

Case#: Patient 42, 1 years old (age at report), female, Indian

DiseaseAssertion: MPS1-H

FamilyInfo: N/A

CasePresentingHPOs: Coarse facial features, joint contractures, corneal clouding, dysostosis multiplex (HP:0000280, HP:0002828, HP:0007957, HP:0000943)

CaseHPOFreeText: N/A

CaseNotHPOs: N/A

CaseNotHPOFreeText: N/A

CaseEnzymeAssay: 3.1% (Range of residual enzyme activity: 0.0%-4.8%)

CaseUrineGAGs: N/A

CaseERT: N/A

CaseBMT: N/A

Variant1: c.1855C>T (p.Arg619Ter)

Variant1ClinVarID: 280976

Variant1CAID: CA2802455

Variant2: c.1855C>T (p.Arg619Ter)

Variant2ClinVarID: 280976

Variant2CAID: CA2802455

AdditionalVariants: N/A

ParentalGenotype: N/A

PreviouslyPublished N/A

Case#: Patient 37, 1 years old (age at report), female, Indian

DiseaseAssertion: MPS1-H

FamilyInfo: N/A

CasePresentingHPOs: Coarse facial features, joint contractures, corneal clouding, dysostosis multiplex (HP:0000280, HP:0002828, HP:0007957, HP:0000943)

CaseHPOFreeText: N/A

CaseNotHPOs: N/A

CaseNotHPOFreeText: N/A

CaseEnzymeAssay: 4.8% (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 28, 8 months old (age at report), female, Indian

DiseaseAssertion: MPS1-H

FamilyInfo: N/A

CasePresentingHPOs: Coarse facial features, hepatosplenomegaly, corneal clouding, dysostosis multiplex (HP:0000280, HP:0001433, HP:0007957, HP:0000943)

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.1273delC (p.His425Thrfs*15)

Variant1ClinVarID: 3391381

Variant1CAID: CA2586965976

Variant2: c.1273delC (p.His425Thrfs*15)

Variant2ClinVarID: 556156

Variant2CAID: CA2586965976

AdditionalVariants: N/A

ParentalGenotype: N/A

PreviouslyPublished N/A

Case#: Patient 50, 2 years old (age at report), female, 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: N/A

CaseNotHPOs: N/A

CaseNotHPOFreeText: N/A

CaseEnzymeAssay: 2.2% (Range of residual enzyme activity: 0.0%-4.8%)

CaseUrineGAGs: N/A

CaseERT: N/A

CaseBMT: N/A

Variant1: c.238G>T (p.Val80Phe)

Variant1ClinVarID: N/A

Variant1CAID: CA355946451

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

Variant2ClinVarID: 956890

Variant2CAID: CA2802083

AdditionalVariants: N/A

ParentalGenotype: N/A

PreviouslyPublished N/A

Case#: Patient 10, 1 years old (age at report), male, Indian

DiseaseAssertion: MPS1-H

FamilyInfo: Sibling of patient 11

CasePresentingHPOs: Coarse facial features, recurrent infections, dysostosis multiplex, intellectual disability, hernia (HP:0000280, HP:0002719, HP:0000943, HP:0001249, 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.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 30, 8 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 (HP:0000280, HP:0001433, HP:0002828, HP:0007957, HP:0002719, HP:0000943, HP:0001249)

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.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 51, 2 years old (age at report), female, Indian

DiseaseAssertion: MPS1-H

FamilyInfo: N/A

CasePresentingHPOs: Coarse facial features, hepatosplenomegaly, joint contractures, dysostosis multiplex (HP:0000280, HP:0001433, HP:0002828, HP:0000943)

CaseHPOFreeText: Cardiac disease

CaseNotHPOs: N/A

CaseNotHPOFreeText: N/A

CaseEnzymeAssay: 2.4% (Range of residual enzyme activity: 0.0%-4.8%)

CaseUrineGAGs: N/A

CaseERT: N/A

CaseBMT: N/A

Variant1: c.265G>C in the article - incorrect variant but unknown what the correct nomenclature is. Could be c.265C>G (p.Arg89Gly) or c.266G>C (p.Arg89Pro)

Variant1ClinVarID: N/A

Variant1CAID: N/A

Variant2: c.779C>T (p.Ser260Phe)

Variant2ClinVarID: 3895951

Variant2CAID: CA355962251

AdditionalVariants: N/A

ParentalGenotype: N/A

PreviouslyPublished N/A

Case#: Family 23, UK

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.1139A>G (p.Q380R)

Variant1ClinVarID: 550799

Variant1CAID: CA2802202

Variant2: c.1861C>T (p.R621X)

Variant2ClinVarID: 11917

Variant2CAID: CA256118

AdditionalVariants: N/A

ParentalGenotype: N/A

PreviouslyPublished N/A

Case#: Family 13, 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.386-2A>G; c.474-2A>G in the paper

Variant1ClinVarID: 222994

Variant1CAID: CA356991

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

Variant2ClinVarID: 280976

Variant2CAID: CA2802455

AdditionalVariants: N/A

ParentalGenotype: N/A

PreviouslyPublished N/A

Case#: Family 9, 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.208C>T (p.Q70X)

Variant1ClinVarID: 11909

Variant1CAID: CA204563

Variant2: c.540_544del (p.W180X); c.628del5 in the paper

Variant2ClinVarID: 3775043

Variant2CAID: CA2573332240

AdditionalVariants: N/A

ParentalGenotype: N/A

PreviouslyPublished N/A

This paper was listed on the ClinVar entry for this variant; however it was only included to show that loss-of-function variants in IDUA are known to be pathogenic

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#: 18, Male, 1.3 years (diagnosed), 9.2 years (report), 20 kg (weight), 89 cm (height), Iranian

DiseaseAssertion: Scheie Syndrome

FamilyInfo: Parents are consanguineous

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

CaseHPOFreeText: HM/HSM

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

CaseNotHPOFreeText: Chronic Rhinorrhea, Cardiac Manifestations

CaseEnzymeAssay: IDUA activity 1.67 (μmol/spot.20h)

CaseUrineGAGs: Quantitative urinary GAG 7.7 (mg/gCr)

CaseERT: N/A

CaseBMT: N/A

GenotypingMethod: Sanger Sequencing

Variant1: p.S157P

Variant2: N/A

AdditionalVariants: N/A

ParentalGenotype: N/A

PreviouslyPublished: N/A

PMID: 31386236

Gene: IDUA

Disease: MPS1

Inheritance: Autosomal recessive

Case#: 14, Male, 0.7 years (diagnosed), 8.5 years (report), 9.5 kg (weight), 73 cm (height), Iranian

DiseaseAssertion: Hurler-Scheie Syndrome

FamilyInfo: Parents are consanguineous

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

CaseHPOFreeText: HM/HSM

CaseNotHPOs: HP:0001249, HP:0000943, HP:0001387, HP:0000365, HP:0007957, HP:0000238 (Mental Retardation, Multiple Dysostosis, Joint Stiffness, Deafness, Corneal Opacity, Hydrocephalus)

CaseNotHPOFreeText: Chronic Rhinorrhea, Cardiac Manifestations

CaseEnzymeAssay: IDUA activity 0.6 (μmol/spot.20h)

CaseUrineGAGs: Quantitative urinary GAG 6.4 (mg/gCr)

CaseERT: N/A

CaseBMT: N/A

GenotypingMethod: Sanger Sequencing

Variant1: p.Y109H

Variant2: N/A

AdditionalVariants: N/A

ParentalGenotype: N/A

PreviouslyPublished: N/A

Case#: 9, Female, 0.7 years (diagnosed), 1.2 years (report), 6.8 kg (weight), 69 cm (height), Iranian

DiseaseAssertion: Hurler-Scheie Syndrome

FamilyInfo: Parents are consanguineous

CasePresentingHPOs: HP:0100790 (Hernia)

CaseHPOFreeText: HM/HSM, Chronic Rhinorrhea

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

CaseNotHPOFreeText: Cardiac Manifestations

CaseEnzymeAssay: IDUA activity 0.97 (μmol/spot.20h)

CaseUrineGAGs: Quantitative urinary GAG 7.21 (mg/gCr)

CaseERT: N/A

CaseBMT: N/A

GenotypingMethod: Sanger Sequencing

Variant1: p.Y109H

Variant2: 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: G219E

Variant1ClinVarID:

Variant1CAID: CA355962006

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: D349N

Variant1ClinVarID: 92623

Variant1CAID: CA220497

Variant2: N/A

Variant2ClinVarID: N/A

Variant2CAID: N/A

AdditionalVariants: N/A

ParentalGenotype: N/A

PreviouslyPublished: N/A

PMID: 24036510

Gene: IDUA

Disease: MPS1

Inheritance: Autosomal recessive

Why Insufficient: Variants are not linked to probands. This paper is assessing IDUA mutations on the structure of alpha-L-iduronidase. Therefore they are pulling common IDUA variants and using them to assess structure, rather than investigating how a variant has impacted a proband.

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: H82Q

Variant1ClinVarID:

Variant1CAID: CA355946477

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: M133I

Variant1ClinVarID:

Variant1CAID: CA91166179

Variant2: N/A

Variant2ClinVarID: N/A

Variant2CAID: N/A

AdditionalVariants: N/A

ParentalGenotype: N/A

PreviouslyPublished: N/A

Case#: One patient from Norway

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.223G>C (p.A75T)

Variant1ClinVarID: 222993

Variant1CAID: CA356994

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

Variant2ClinVarID: 11908

Variant2CAID: CA220498

AdditionalVariants: N/A

ParentalGenotype: N/A

PreviouslyPublished N/A

Case#: Patient 3, female, 18.1 months (age at diagnosis), 31 months (age at HSCT), 7 MRI + neuropsychological observations over the course of 16 years.

DiseaseAssertion: MPS-1H

FamilyInfo: N/A

CasePresentingHPOs: N/A

CaseHPOFreeText: N/A

CaseNotHPOs: N/A

CaseNotHPOFreeText: N/A

CaseEnzymeAssay: 43.5 nmol/h/mg (Normal values: 11-43 nmol/h/mg)

CaseUrineGAGs: N/A

CaseERT: N/A

CaseBMT: Yes

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#: PKMPS1P10, 4 years old (age at presentation), female, Pakastani

DiseaseAssertion: MPS-I

FamilyInfo: One of her elder siblings died due to MPS-I and her parents were cousins.

CasePresentingHPOs: Coarse facial features (HP:0000256)

CaseHPOFreeText: Poor growth potential, underweight, stunted and widening of the wrist

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#: PKMPS1P2a, 8 years old (age at presentation), female, Pakastani

DiseaseAssertion: MPS-IH

FamilyInfo: Proband has an affected younger brother (PKMPS1P2b)

CasePresentingHPOs: On and off snoring, nasal congestion, failure to thrive, abdominal distension, recurrent respiratory infections, hepatomegaly (HP:0025267, HP:0001742, HP:0001508, HP:0003270, HP:0002788, HP:0002240)

CaseHPOFreeText: A liver span of 2 cm with firm consistency and a smooth surface. Smooth muscle infections.

CaseNotHPOs: Vomiting, headache (HP:0002013, HP:0002315)

CaseNotHPOFreeText: Fever, difficulty walking, normal facial features and normal eyes.

CaseEnzymeAssay: N/A

CaseUrineGAGs: N/A

CaseERT: N/A

CaseBMT: N/A

Variant1: c.908T>C (p.L303P)

Variant1ClinVarID: N/A

Variant1CAID: CA355962537

Variant2: c.908T>C (p.L303P)

Variant2ClinVarID: N/A

Variant2CAID: CA355962537

AdditionalVariants: N/A

ParentalGenotype: N/A

PreviouslyPublished N/A

Case#: Patient 24, born in 2009 (paper published in 2017), 8 months (age at first treatment)

DiseaseAssertion: MPSI-H

FamilyInfo: N/A

CasePresentingHPOs: Corneal clouding (HP:0007957)

CaseHPOFreeText: N/A

CaseNotHPOs: Cataract, retinopathy (HP:0000518, HP:0000488)

CaseNotHPOFreeText: N/A

CaseEnzymeAssay: 48.88 ng/mol (48.75 weight matched enzyme reference assay)

CaseUrineGAGs: 0.28 DS/CS

CaseERT: Yes

CaseBMT: Yes, MUD

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

Variant1ClinVarID: 11908

Variant1CAID: CA220498

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

Variant2ClinVarID: 11909

Variant2CAID: CA204563

AdditionalVariants: N/A

ParentalGenotype: N/A

PreviouslyPublished N/A

Case#: Patient 7, born in 2005 (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: 62.57 ng/mol (34.3 weight matched enzyme reference assay)

CaseUrineGAGs: 0.59 DS/CS

CaseERT: No

CaseBMT: Yes, Cord

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

Variant1ClinVarID: 11908

Variant1CAID: CA220498

Variant2: c.386-2A>G

Variant2ClinVarID: 222994

Variant2CAID: CA356991

AdditionalVariants: N/A

ParentalGenotype: N/A

PreviouslyPublished N/A

Case#: Patient 2, born in 2000 (paper published in 2017), 18 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: 28 ng/mol (38 weight matched enzyme reference assay)

CaseUrineGAGs: 0.36 DS/CS

CaseERT: No

CaseBMT: Yes, MUD

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

Variant1ClinVarID: 11908

Variant1CAID: CA220498

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

Variant2ClinVarID: 167190

Variant2CAID: CA234128

AdditionalVariants: N/A

ParentalGenotype: N/A

PreviouslyPublished N/A

Case#: Patient 6, 5 years old, Iranian

DiseaseAssertion: MPSI-H (Severe)

FamilyInfo: N/A

CasePresentingHPOs: N/A

CaseHPOFreeText: N/A

CaseNotHPOs: N/A

CaseNotHPOFreeText: N/A

CaseEnzymeAssay: 0.05 µmol/g.h (Normal ranges: 10-50 µmol/g.h)

CaseUrineGAGs: N/A

CaseERT: N/A

CaseBMT: N/A

Variant1: c.590-17_607del (GFLNYY197-202)

Variant1ClinVarID: N/A

Variant1CAID: CA2586973524

Variant2: c.590-17_607del (GFLNYY197-202)

Variant2ClinVarID: N/A

Variant2CAID: CA2586973524

AdditionalVariants: N/A

ParentalGenotype: N/A

PreviouslyPublished N/A

Case#:Patient Sample unique ID 37, Infant screened positive at birth (specimens with activity ≤15% of the DMA for enzyme activity and a CLIR screening algorithm result of indeterminate or MPS I)

DiseaseAssertion:None

FamilyInfo:None

CasePresentingHPOs:None

CaseHPOFreeText:None

CaseNotHPOs:None

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

CaseEnzymeAssay: IDUA activity 0.629 (13.9) umol/L/h (%DMA) during new born screening through dried blood spot (plasma) and 13.9 pmol/punch/h Confirmatory IDUA enzyme

CaseUrineGAGs: DS 3.4 g/mol creatinine and HS 2.7 g/mol creatinine (Normal)

CaseERT:No

CaseBMT:No

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

Variant1ClinVarID:41682

Variant1CAID: CA000358

Variant2:heterozygous PD: c.246C>G; p.H82Q

Variant2ClinVarID:92637

Variant2CAID:CA220506

AdditionalVariants: None

ParentalGenotype:None provided

PreviouslyPublished:N/A

Case#:Patient Sample unique ID 67, Infant screened positive at birth (specimens with activity ≤15% of the DMA for enzyme activity and a CLIR screening algorithm result of indeterminate or MPS I)

DiseaseAssertion:None

FamilyInfo:None

CasePresentingHPOs:None

CaseHPOFreeText:None

CaseNotHPOs:None

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

CaseEnzymeAssay: IDUA activity 0.454 (5.9) umol/L/h (%DMA) during new born screening through dried blood spot (plasma) and 8.8 pmol/punch/h Confirmatory IDUA enzyme

CaseUrineGAGs: DS 4.2 g/mol creatinine and HS 4.7 g/mol creatinine (Normal)

CaseERT:No

CaseBMT:No

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

Variant1ClinVarID:41682

Variant1CAID: CA000358

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

Variant2ClinVarID:53610

Variant2CAID:CA326991

AdditionalVariants:None

ParentalGenotype:None provided

PreviouslyPublished:N/A

Case#: Patient 2, female, 18 months (age at diagnosis), 22 months (age at HSCT), weight of 12.1 kg (at HSCT), 5 years (age at report). Neurological development is not impaired.

DiseaseAssertion: MPS1-H

FamilyInfo: N/A

CasePresentingHPOs: Coarse facial features, kyphosis, abdominal distension, mild mitral regurgitation (HP:0000256, HP:0002808, HP:0003270, HP:0001653)

CaseHPOFreeText: Chronic hydrocephalus-VP-shunt

CaseNotHPOs: N/A

CaseNotHPOFreeText: N/A

CaseEnzymeAssay: Activity of alpha-L-iduronidase in leukocytes was normal from 5 months after cessation of ERT.

CaseUrineGAGs: Patient had normal excretion of total urine GAGs - but a small fraction of dermatansulfate remained detectable upon electrophoresis of total urinary GAGs.

CaseERT: Yes - 13 weeks of ERT before HSCT. Continued until day 50 of HSCT.

CaseBMT: Yes - interval diagnosis for HSCT (15 weeks). The donor was female and unrelated.

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

Variant1ClinVarID: 11909

Variant1CAID: CA204563

Variant2: c.1631_1640del

Variant2ClinVarID: N/A

Variant2CAID: CA1433071867

AdditionalVariants: N/A

ParentalGenotype: N/A

PreviouslyPublished N/A

Case#: 0.2% residual activity at 37 °C

DiseaseAssertion: MPS1-H

FamilyInfo: N/A

CasePresentingHPOs: N/A

CaseHPOFreeText: N/A

CaseNotHPOs: N/A

CaseNotHPOFreeText: N/A

CaseEnzymeAssay: 0.5 ± 0.1 nmol/mg/h IDUA activity at 37 °C

CaseUrineGAGs: N/A

CaseERT: N/A

CaseBMT: N/A

Variant1: c.979G>A (p.A327P)

Variant1ClinVarID: 167190

Variant1CAID: CA234128

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

ClinVarID: 167190

Variant2CAID: CA234128

AdditionalVariants: N/A

ParentalGenotype: N/A

PreviouslyPublished N/A

Case#: <0.1% residual activity at 37 °C

DiseaseAssertion: MPS1-H

FamilyInfo: N/A

CasePresentingHPOs: N/A

CaseHPOFreeText: N/A

CaseNotHPOs: N/A

CaseNotHPOFreeText: N/A

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

CaseUrineGAGs: N/A

CaseERT: N/A

CaseBMT: N/A

Variant1: c.134del12 on paper but nomenclature is c.46_57del (p.Ser16_Ala19del)

Variant1ClinVarID: 92643

Variant1CAID: CA220509

Variant2: c.134del12 on paper but nomenclature is c.46_57del (p.Ser16_Ala19del)

ClinVarID: 92643

Variant2CAID: CA220509

AdditionalVariants: N/A

ParentalGenotype: N/A

PreviouslyPublished N/A

PMID: 35619307

Gene: IDUA

Disease: MPS1

Inheritance: Autosomal recessive

Case#: Male, 2-year old

DiseaseAssertion: MPS1-H

FamilyInfo: Not provided

CasePresentingHPOs: Not provided

CaseHPOFreeText: NA

CaseNotHPOs: Not provided

CaseNotHPOFreeText: NA

CaseEnzymeAssay: MPS1-H fibroblasts exhibited no activity of IDUAα (0.01 ± 0.02 nmol/mg/min); iPSC clones were devoid of IDUAα activity

CaseUrineGAGs: Not provided

CaseERT: Don't know

CaseBMT: Don't know

Variant1: NM_000203.5(IDUA):c.1073_1093del (p.His358_Thr364del)

Variant1ClinVarID:557260

Variant1CAID:

Variant2: NM_000203.4(IDUA):c.1205 G>A (p.Trp402Ter)

Variant2ClinVarID:11908

Variant2CAID:

ParentalGenotype: Not provided

PreviouslyPublished: Authors reference [30]: PMID: 31678774 DOI: 10.1016/j.scr.2019.101604

PMID: 10735634

Gene: IDUA

Disease: MPS1

Inheritance: Autosomal recessive

PMID: 26750310 Gene: IDUA Disease: MPS1 Inheritance: Autosomal recessive

Case#: Patient F (female), diagnosed at 4 years and 6 months on the basis of clinical findings, an elevated urinary glycosaminoglycan level, and low α-l-iduronidase activity in leukocytes. Patient F was 104.0 cm tall (75th percentile).

DiseaseAssertion: MPS1-H/S

FamilyInfo: The patient is an older sibling who was diagnosed with the disease and has an affected younger brother.

CasePresentingHPOs: Coarse facial features, joint stiffness, thick skin, corneal clouding, hepatosplenomegaly, dysostosis multiplex (HP:0000280, HP:0001387, HP:0001072, HP:0007957, HP:0001433, HP:0000943)

CaseHPOFreeText: Moderate mitral insufficiency with thickened valve leaflets and anterior edge prolapse; mild left atrium thickening and increased pulmonary pressure were also present. Radiographic skeletal examination showed several signs of hip hypoplasia, ovoid shape of lumbar vertebral bodies, V-shaped distal ulnar and radial extremities, and short and broad metacarpal bones. Although she had normal intelligence, she developed obstructive hydrocephalus, which required shunting at 7 months of age.

CaseNotHPOs: N/A

CaseNotHPOFreeText: N/A

CaseEnzymeAssay: Low α-l-iduronidase activity in leukocytes

CaseUrineGAGs: Elevated urinary glycosaminoglycan levels

CaseERT: Yes - Patient F started laronidase at 5 years of age, also at the standard dose. After 5 years of therapy, she was 138.0 cm tall (90th percentile), her liver and spleen volume had normalized, her skin had become less thickened, and her shoulder flexion and extension were moderately improved. Her dysostosis multiplex, cardiac function, and corneal clouding (visual acuity: 10/10) had stabilized but were not improved.

CaseBMT: N/A

Variant1: c.12205G>A (p.W402X)

Variant1ClinVarID: 11908

Variant1CAID: CA220498

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

Variant2ClinVarID: 638076

Variant2CAID: CA355965038

AdditionalVariants: N/A

ParentalGenotype: N/A

PreviouslyPublished N/A

Case#: Patient 27, female, Han origin, 9 years old (age at diagnosis)

DiseaseAssertion: MPS1-H/S

FamilyInfo: N/S

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

CaseHPOFreeText: N/A

CaseNotHPOs: Global Developmental Delay, Macrocephaly, Hernia (HP:0001263, HP:0000256, HP:0100790)

CaseNotHPOFreeText: Cardiac disease

CaseEnzymeAssay: IDUA activity 3.4 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.98A>C (p.H33P)

Variant1ClinVarID: N/A

Variant1CAID: CA355945475

Variant2: c.1402+2T>G

Variant2ClinVarID: 553131

Variant2CAID: CA355964392

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 21, female, Han origin, 10 years old (age at diagnosis)

DiseaseAssertion: MPS1-S

FamilyInfo: N/A

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

CaseHPOFreeText: N/A

CaseNotHPOs: Global Developmental Delay, Macrocephaly, Mongolian macula (HP:0001263, HP:0000256, HP:0011369)

CaseNotHPOFreeText: Cardiac disease

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.1898C>T (p.S633L)

Variant1ClinVarID: 556406

Variant1CAID: CA355966010

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

Variant2ClinVarID: 556358

Variant2CAID: CA355961718

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 36, female, Han origin, 5 years old (age at diagnosis)

DiseaseAssertion: MPS1-H/S

FamilyInfo: N/A

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

CaseHPOFreeText: N/A

CaseNotHPOs: Global Developmental Delay, Mongolian macula, Hernia, (HP:0001263, HP:0011369, HP:0100790)

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.159C>A (p.C53X)

Variant1ClinVarID: 1458768

Variant1CAID: N/A

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

Variant2ClinVarID: 11927

Variant2CAID: CA256128

AdditionalVariants: N/A

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

PreviouslyPublished N/A

Case#: Patient 43, male, Han origin, 5 years old (age at diagnosis)

DiseaseAssertion: MPS1-H/S

FamilyInfo: N/A

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

CaseHPOFreeText: N/A

CaseNotHPOs: Global Developmental Delay, Macrocephaly (HP:0001263, HP:0000256)

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.300-3C>G

Variant1ClinVarID: 551563

Variant1CAID: CA549265042

Variant2: c.530dupT (p.Glu178ArgfsTer5) (Paper refers to the variant as c.531dupT, there is a typo in the article where all duplication variants are one base pair off)

Variant2ClinVarID: N/A

Variant2CAID: CA2586973520

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

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 No. 2 (Table 1), Arabic Druze ethnic group, male, 1.15 years old (age at time of gene therapy), 100 IQ score, 2.40 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.192C>A (p.Y64X)

Variant1ClinVarID: 11914

Variant1CAID: CA256113

Variant2: c.192C>A (p.Y64X)

Variant2ClinVarID: 11914

Variant2CAID: CA256113

AdditionalVariants: N/A

ParentalGenotype: N/A

PreviouslyPublished N/A

Case#: Patient No. 7 (Table 1), Black race, male, 1.71 years (age at time of gene therapy), 80 IQ score, 1.73 years since gene therapy (1.5 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.923_926delTGCC (p.L308HfsX8)

Variant1ClinVarID: N/A

Variant1CAID: N/A

Variant2: c.923_926delTGCC (p.L308HfsX8)

Variant2ClinVarID: N/A

Variant2CAID: N/A

AdditionalVariants: N/A

ParentalGenotype: N/A

PreviouslyPublished N/A

PMID: 34788506

Gene: IDUA

Disease: MPS1

Inheritance: Autosomal recessive

Case#: Patient 32, Italy

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.1205G>A (p.W402X)

Variant1ClinVarID: 11908

Variant1CAID: CA220498

Variant2: c.1225G>A (p.G265R)

Variant2ClinVarID: 1084956

Variant2CAID: CA91169920

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

Case#: Patient 10, Italy

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.1205G>A (p.W402X)

Variant1ClinVarID: 11908

Variant1CAID: CA220498

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

Variant2ClinVarID: 638076

Variant2CAID: CA355865038

AdditionalVariants: N/A

ParentalGenotype: N/A

PreviouslyPublished N/A

Case#: Patient 65, 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.979G>C (p.A327P)

Variant1ClinVarID: 167190

Variant1CAID: CA234128

Variant2: c.1154C>G (p.P385R)

Variant2ClinVarID: 556024

Variant2CAID: CA355963438

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.1225G>A (p.G409R)

Variant1ClinVarID: 1084956

Variant1CAID: CA91169920

Variant2: c.1757C>T (p.S386F)

Variant2ClinVarID: 571910

Variant2CAID: CA2802396

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.1148G>A (p.R383H)

Variant1ClinVarID: 558189

Variant1CAID: CA2802205

Variant2: c.112C>A (p.R89S)

Variant2ClinVarID: 2432781

Variant2CAID: CA355945526

AdditionalVariants: c.250G>A (p.G48S), ClinVarID:726495, CAID:CA2801152

ParentalGenotype: N/A

PreviouslyPublished N/A

Case#: No additional case information provided

DiseaseAssertion: MPSI-H/S

FamilyInfo: N/A

CasePresentingHPOs: N/A

CaseHPOFreeText: N/A

CaseNotHPOs: N/A

CaseNotHPOFreeText: N/A

CaseEnzymeAssay: Abnormal

CaseUrineGAGs: Normal

CaseERT: N/A

CaseBMT: N/A

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

Variant1ClinVarID: 11909

Variant1CAID: CA220498

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

Variant2ClinVarID: 567566

Variant2CAID: CA2802300

AdditionalVariants: N/A

ParentalGenotype: N/A

PreviouslyPublished N/A

Case#: Patient #3 (see Table 2), male, 15 months old (age at diagnosis), 5 years old (age at report).

DiseaseAssertion: MPS-I

FamilyInfo: Born to a consanguineous family

CasePresentingHPOs: Macrocephaly, corneal clouding, hearing loss (HP:0000256, HP:0007957, HP:0000365)

CaseHPOFreeText: Normal intelligence

CaseNotHPOs: N/A

CaseNotHPOFreeText: N/A

CaseEnzymeAssay: α-L-iduronidase 15.6 pmol/spot. The activity of this enzyme is below its reference (200–2600 pmol/spot).

CaseUrineGAGs: N/A

CaseERT: N/A

CaseBMT: N/A

Variant1: c.1A>C (p.M1L)

Variant1ClinVarID: 550458

Variant1CAID: CA355945204

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

Variant2ClinVarID: N/A

Variant2CAID: CA355961573

AdditionalVariants: N/A

ParentalGenotype: Variant c.1A>C was paternally inherited and variant c.469T>C was maternally inherited.

PreviouslyPublished N/A

This is a review article that focuses on the prevalence of IDUA variants. The IDUA variants are not linked to specific patients or patient descriptions.

Case#: Pt 106 , Age 24 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#: 207 5.9 yrs male, age at initial diagnosis 2.6 yrs DiseaseAssertion: MPS IH FamilyInfo:Nil CasePresentingHPOs: CaseHPOFreeText: CaseNotHPOs: CaseNotHPOFreeText: CaseEnzymeAssay: IDUA activity: low leukocyte IDUA enzyme activity CaseUrineGAGs: CaseERT: 3 yrs on ERT, then study drug, valanafusp alpha, also called AGT-181 for 12 months

CaseBMT: No PreviouslyPublished Don't know Variant1:p.Q70X Variant1ClinVarID: 11909 Variant1CAID: CA204563 Variant2:p.W402X Variant2ClinVarID: 11908 Variant2CAID: CA220498

Case#: Pt2, Male, 15 months (diagnosis), 15 months (onset)

DiseaseAssertion: Hurler Syndrome

FamilyInfo: N/A Pedigree (Figure 4Pt2)

CasePresentingHPOs: HP:0000280, HP:0000365, HP:0001654, HP:0100814, (Coarse face, Hearing Loss, Valvular heart disease, Dermal melanocytosis)

CaseHPOFreeText: N/A

CaseNotHPOs: HP:0007957, HP:0001387, HP:0001433, (Cornea clouding, Joint stiffness, Hepatosplenomegaly)

CaseNotHPOFreeText: Long bone deformation, Spinal deformation, Inguinal or Umbilical hernia

CaseEnzymeAssay: α-L-iduronidase 0.06 (dried blood spots, normal >1.32 µM/h)

CaseUrineGAGs: Urine heparan sulfate 55.44 (mg/mmol creatinine) {0.65-3.51}

CaseERT: N/A

CaseBMT: N/A

GenotypingMethod: Not Provided.

Variant1: c.1190-10C>A

Variant1ClinVarID: 950888

Variant1CAID: CA1139658405

Variant2: c.1190-10C>A

Variant2ClinVarID: 950888

Variant2CAID: CA1139658405

AdditionalVariants: N/A

ParentalGenotype: Both parents are homozygous for not having the c.1190-10C>A variant (figure 4 Pt 2)

PreviouslyPublished: N/A

Case#: Pt1, Male, 20 months (diagnosis), 20 months (onset)

DiseaseAssertion: Hurler Syndrome

FamilyInfo: N/A Pedigree (Figure 4Pt1)

CasePresentingHPOs: HP:0000280, HP:0007957, HP:0001654, HP:0100814, (Coarse face, Cornea clouding, Valvular heart disease, Dermal melanocytosis)

CaseHPOFreeText: N/A

CaseNotHPOs: HP:0001387, HP:0000365, HP:0001433, (Joint stiffness, Hearing loss, Hepatosplenomegaly)

CaseNotHPOFreeText: Long bone deformation, Spinal deformation, Inguinal or umbilical hernia

CaseEnzymeAssay: α-L-iduronidase 0.17 (dried blood spots, normal >1.32 µM/h)

CaseUrineGAGs: Urine heparan sulfate 8.26 (mg/mmol creatinine) {<0.67}

CaseERT: N/A

CaseBMT: N/A

GenotypingMethod: Not Provided.

Variant1: c.1190-10C>A

Variant1ClinVarID: 950888

Variant1CAID: CA1139658405

Variant2: c.1190-10C>A

Variant2ClinVarID: 950888

Variant2CAID: CA1139658405

AdditionalVariants: N/A

ParentalGenotype: Both parents are homozygous for not having the c.1190-10C>A variant (figure 4 Pt 1)

PreviouslyPublished: N/A

Case#: Patient 1, male, 1 year old (age at diagnosis), 2 years old (age when deceased - due to a severe respiratory infection)

DiseaseAssertion: MPS I-H

FamilyInfo: Parents had a consanguineous marriage

CasePresentingHPOs: Coarse facial features, corneal clouding, hepatosplenomegaly, skeletal dysplasia, global developmental delay (HP:0000280, HP:0007957, HP:0001433, HP:0002652, HP:0001263)

CaseHPOFreeText: N/A

CaseNotHPOs: N/A

CaseNotHPOFreeText: N/A

CaseEnzymeAssay: N/A

CaseUrineGAGs: N/A

CaseERT: N/A

CaseBMT: N/A

Variant1: c.252insC (current nomenclature: c.252dup)

Variant1ClinVarID: N/A

Variant1CAID: CA3060586149

Variant2: c.252insC (current nomenclature: c.252dup)

Variant2ClinVarID: N/A

Variant2CAID: CA3060586149

AdditionalVariants: N/A

ParentalGenotype: N/A

PreviouslyPublished N/A

PMID: 32781600 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.1858G>T (p.V620F)

Variant1ClinVarID: 1067173

Variant1CAID: CA355965934

Variant2: c.1858G>T (p.V620F)

Variant2ClinVarID: 1067173

Variant2CAID: CA355965934

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.1205G>A (p.W402X)

Variant1ClinVarID: 11908

Variant1CAID: CA220498

Variant2: c.1650+5G>A

Variant2ClinVarID: 92634

Variant2CAID: CA220504

AdditionalVariants: N/A

ParentalGenotype: N/A

PreviouslyPublished N/A

Case#: P2, Female, 8.7 years (diagnosed), 10.7 (report), 21 kg (weight), 122 cm (height), Algerian

DiseaseAssertion: Scheie Syndrome

FamilyInfo: Parents are consanguineous

CasePresentingHPOs: HP:0001999, HP:0000943, HP:0001387, HP:0000365, HP:0007957, HP:0000238 (Facial Dysmorphic Features, Multiple Dysostosis, Hernia(Ombelical), Deafness(bilateral transmission), Corneal Opacity, Hydrocephalus)

CaseHPOFreeText: Chronic Rhinorrhea, Cardiac Manifestations(Mitral Insufficiency & Aortic Insufficiency)

CaseNotHPOs: HP:0001249, HP:0002240 (Mental Retardation, Joint Stiffness)

CaseNotHPOFreeText: HM/HSM

CaseEnzymeAssay: IDUA Enzyme activity 0 (% to the reference range mean)

CaseUrineGAGs: GAG quantitation 47 (fold change to the reference range mean according to age)

CaseERT: N/A

CaseBMT: N/A

GenotypingMethod: Direct DNA Fragments Sequencing

Variant1: c.1598C>G (p.Pro533Arg)

Variant1ClinVarID: 11910

Variant1CAID: CA256112

Variant2: c.1598C>G (p.Pro533Arg)

Variant2ClinVarID: 11910

Variant2CAID: CA256112

AdditionalVariants: N/A

ParentalGenotype: N/A

PreviouslyPublished N/A

PMID: 32162878

Gene: IDUA

Disease: MPS1

Inheritance: Autosomal recessive

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 9 (see Table 1), 5 years old - deceased (age at report), 1 year old (age at onset), female, height of 102 cm, weight of 18 kg, located at Mahdia: Touristic region.

DiseaseAssertion: MPS1 - severe

FamilyInfo: Parents were 1st cousins (see Table 2), aged 50 yrs (M) and 62 yrs (F).

CasePresentingHPOs: HP:0004322, HP:0010864, HP:0001537, HP:0000687, HP:0030812, HP:0001999, HP:0007957, HP:0000943 (Short stature, severe intellectual disability, umbilical hernia, widely spaced teeth, enlarged tonsils, facial dysmorphia, corneal clouding, dysostosis multiplex)

CaseHPOFreeText: Pigmented skin

CaseNotHPOs: N/A

CaseNotHPOFreeText: N/A

CaseEnzymeAssay: IDUA activity 0.020 μKat/kg

CaseUrineGAGs: N/A

CaseERT: N/A

CaseBMT: N/A

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

Variant1ClinVarID: 550421

Variant1CAID: CA2802462

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

Variant2ClinVarID: 550421

Variant2CAID: CA2802462

AdditionalVariants: N/A

ParentalGenotype: N/A

PreviouslyPublished N/A

Case#: Patient 4 (see Table 1), 9 years - deceased (age at report), 7 months (age at onset), male, height of 107 cm, weight of 19 kg, location at Gabes: Industrial region.

DiseaseAssertion: MPS1 - severe

FamilyInfo: One affected siblings (Patient 5), parents were 1st cousins (see Table 2) aged 55 yrs (M) and 65 yrs (F).

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

CaseHPOFreeText: N/A

CaseNotHPOs: N/A

CaseNotHPOFreeText: N/A

CaseEnzymeAssay: IDUA activity: 0.018 μKat/kg

CaseUrineGAGs: N/A

CaseERT: N/A

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#: Female, 6 years old (age of onset), 8 years old (age at report). Developmentally normal at 6 years old but had a 1-year long history of painful and stiff joints. Her weight was in the 5th percentile, height in the 3rd percentile, and head circumference in the 10th percentile for her age group.

DiseaseAssertion: MPS1-S

FamilyInfo: The patient's parents are second cousins. She has two healthy brothers.

CasePresentingHPOs: Joint stiffness, recurrent otitis media, snoring, joint contractures, carpal tunnel syndrome (HP:0001387, HP:0000403, HP:0025267, HP:0100790, HP:0012185)

CaseHPOFreeText: Painful joints affecting the hands, wrists, knees, elbows, and shoulders. At 8 years old, she had second and third finger numbness. Flexion contractures in distal and proximal interphalangeal joints, wrists, and restricted joint mobility was observed. Echocardiogram showed thickening of the mitral and aortic valves, and brain magnetic resonance imaging demonstrated increased signal in the white matter surrounding dilated perivascular spaces.

CaseNotHPOs: Coarse facial features, cardiac murmurs, hernias (HP:0000256, HP:0030148, HP:0100790)

CaseNotHPOFreeText: Organomegaly

CaseEnzymeAssay: 1 nmol/h/mg (reference range, 14-41 nmol/h/mg)

CaseUrineGAGs: Excess heparan and dermatan sulfate

CaseERT: Enzyme replacement therapy was initiated. Improvements in hand mobility and joint size were noted, as well as less joint discomfort.

CaseBMT: N/A

Variant1: c.1039A>C (p.S347R)

Variant1ClinVarID: 1067172

Variant1CAID: CA355963126

Variant2: c.1039A>C (p.S347R)

Variant2ClinVarID: 1067172

Variant2CAID: CA355963126

AdditionalVariants: N/A

ParentalGenotype: N/A

PreviouslyPublished N/A

annotating here sice the article is only available as a PDF.

Case#: Clarke Patient 3

DiseaseAssertion: MPS I, severe

FamilyInfo: father and mother were het carriers

CasePresentingHPOs:

CaseHPOFreeText: severe clinical phenotype with presentation in the first year of life and currently at age two has received bone marrow transplantation

CaseNotHPOs:

CaseNotHPOFreeText:

GenotypingMethod: SSCP, restriction enzyme digestion

PreviouslyPublished: n/a

Variant: c.820G>T (p.Glu274Ter); Q70X phase confirmed

CAID: CA355962341

SupplementalData: n/a

PMID: 28649516

Gene: IDUA

Disease: MPS1

Inheritance: Autosomal recessive

PMID: 21037085

Gene: IDUA

Disease: MPS1

Inheritance: Autosomal recessive