Case#: Family 11, 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: N/A

Variant2ClinVarID: N/A

Variant2CAID: N/A

AdditionalVariants: N/A

ParentalGenotype: N/A

PreviouslyPublished N/A

Case#: Family 19, Slovenia

DiseaseAssertion: MPS1-H

FamilyInfo: N/A

CasePresentingHPOs: N/A

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

CaseNotHPOs: N/A

CaseNotHPOFreeText: N/A

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

CaseUrineGAGs: N/A

CaseERT: N/A

CaseBMT: N/A

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

Variant1ClinVarID: 11909

Variant1CAID: CA204563

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 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

Case#: Patient 296, female, northern European origin, 8 months (age of diagnosis), 4 years and 9 months (age of death)

DiseaseAssertion: MPS1-H, severe

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.1614del (delG1702)

Variant2ClinVarID: 167191

Variant2CAID: CA234129

AdditionalVariants: N/A

ParentalGenotype: N/A

PreviouslyPublished N/A

Case#: Patient 296, female, northern European origin, 8 months (age of diagnosis), 4 years and 9 months (age of death)

DiseaseAssertion: MPS1-H, severe

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: N/A

Variant2: c.1614del (delG1702)

Variant2ClinVarID: 167191

Variant2CAID: N/A

AdditionalVariants: N/A

ParentalGenotype: N/A

PreviouslyPublished N/A

Case#: Patient 14 (group 2), Poland, male 5 years old (age at diagnosis), 15 years old (age at baseline), 19 years old (current age)

DiseaseAssertion: MPS1-S

FamilyInfo: N/A

CasePresentingHPOs: Limitation of join mobility, joint stiffness (HP:0001376, HP:0001387)

CaseHPOFreeText: Patients in group 2 had normal mental development or only slightly delayed mental development and, therefore, could undergo active physical rehabilitation.

CaseNotHPOs: N/A

CaseNotHPOFreeText: N/A

CaseEnzymeAssay: Diagnosis of MPS I was confirmed by the biochemical determination of α-L-iduronidase activity deficiency in leukocytes and by molecular analysis.

CaseUrineGAGs: N/A

CaseERT: Yes, weekly infusions for 52-208 weeks (depending on the patient)

CaseBMT: N/A

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

Variant1ClinVarID: 11909

Variant1CAID: CA204563

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

Variant2ClinVarID: 638074

Variant2CAID: CA2802098

AdditionalVariants: N/A

ParentalGenotype: N/A

PreviouslyPublished N/A

Case#: Patient 13 (group 2), Poland, male 2 years old (age at diagnosis), 2.5 years old (age at baseline), 6.5 years old (current age)

DiseaseAssertion: MPS1-S

FamilyInfo: N/A

CasePresentingHPOs: Limitation of join mobility, joint stiffness (HP:0001376, HP:0001387)

CaseHPOFreeText: Patients in group 2 had normal mental development or only slightly delayed mental development and, therefore, could undergo active physical rehabilitation.

CaseNotHPOs: N/A

CaseNotHPOFreeText: N/A

CaseEnzymeAssay: Diagnosis of MPS I was confirmed by the biochemical determination of α-L-iduronidase activity deficiency in leukocytes and by molecular analysis.

CaseUrineGAGs: N/A

CaseERT: Yes, weekly infusions for 52-208 weeks (depending on the patient)

CaseBMT: N/A

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

Variant1ClinVarID: 11909

Variant1CAID: CA204563

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

Variant2ClinVarID: 552686

Variant2CAID: CA2801140

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

ParentalGenotype: N/A

PreviouslyPublished N/A

Case#: Patient 36 (Table 3)

DiseaseAssertion: Attenuated naïve MPS 1

FamilyInfo: N/A

CasePresentingHPOs: N/A

CaseHPOFreeText: N/A

CaseNotHPOs: N/A

CaseNotHPOFreeText: N/A

CaseEnzymeAssay: 7 nmol/h/mg per DBS (dried blood spots) determined during NBS. 13 DBS protein concentration determined by Immuno-SRM (pmol/L). 125.50 relative protein abundance, expressed as the ratio between IDUA/GAA (amol / fmol) in buccal swabs.

CaseUrineGAGs: N/A

CaseERT: Yes

CaseBMT: N/A

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

Variant1ClinVarID: 11909

Variant1CAID: CA204563

Variant2: c.1070C>T (p.P357L)

Variant2ClinVarID: 1683228

Variant2CAID: CA91169110

AdditionalVariants: N/A

ParentalGenotype: N/A

PreviouslyPublished N/A

Case#: Patient 35 (Table 3)

DiseaseAssertion: Attenuated naïve MPS 1

FamilyInfo: N/A

CasePresentingHPOs: N/A

CaseHPOFreeText: N/A

CaseNotHPOs: N/A

CaseNotHPOFreeText: N/A

CaseEnzymeAssay: 7 nmol/h/mg per DBS (dried blood spots) determined during NBS. 7.2 DBS protein concentration determined by Immuno-SRM (pmol/L).

CaseUrineGAGs: N/A

CaseERT: Yes

CaseBMT: N/A

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

Variant1ClinVarID: 11909

Variant1CAID: CA204563

Variant2: c.299+5G>T

Variant2ClinVarID: N/A

Variant2CAID: CA549149418

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: 0.2 ± 0.1 nmol/mg/h IDUA activity at 37 °C

CaseUrineGAGs: N/A

CaseERT: N/A

CaseBMT: N/A

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

Variant1ClinVarID: 11909

Variant1CAID: CA204563

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

ClinVarID: 11909

Variant2CAID: CA204563

AdditionalVariants: N/A

ParentalGenotype: N/A

PreviouslyPublished N/A

Case#: 0.2% 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: 0.5 ± 0.1 nmol/mg/h IDUA activity at 37 °C

CaseUrineGAGs: N/A

CaseERT: N/A

CaseBMT: N/A

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

Variant1ClinVarID: 11909

Variant1CAID: CA204563

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

ClinVarID: 558189

Variant2CAID: CA2802205

AdditionalVariants: N/A

ParentalGenotype: N/A

PreviouslyPublished N/A

Case#: Patient 22, born in 1995 (paper published in 2017), 8 months (age at first treatment). 2 years and 2 months (age at last 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: 49.94 ng/mol (38.49 weight matched enzyme reference assay)

CaseUrineGAGs: 0.43 DS/CS

CaseERT: No

CaseBMT: Yes, Sib

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

Variant1ClinVarID: 11909

Variant1CAID: CA204563

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

Variant2ClinVarID: 11909

Variant2CAID: CA204563

AdditionalVariants: N/A

ParentalGenotype: N/A

PreviouslyPublished N/A

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

DiseaseAssertion: MPSI-H

FamilyInfo: N/A

CasePresentingHPOs: Corneal clouding (HP:0007957)

CaseHPOFreeText: N/A

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

CaseNotHPOFreeText: N/A

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

CaseUrineGAGs: 0.4 DS/CS

CaseERT: Yes

CaseBMT: Yes, cord

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

Variant1ClinVarID: 11909

Variant1CAID: CA204563

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

Variant2ClinVarID: 167190

Variant2CAID: CA234128

AdditionalVariants: N/A

ParentalGenotype: N/A

PreviouslyPublished N/A

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

DiseaseAssertion: MPSI-H

FamilyInfo: N/A

CasePresentingHPOs: Corneal clouding (HP:0007957)

CaseHPOFreeText: N/A

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

CaseNotHPOFreeText: N/A

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

CaseUrineGAGs: 0.34 DS/CS

CaseERT: Yes

CaseBMT: Yes, Cord

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

Variant1ClinVarID: 11908

Variant1CAID: CA220498

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

Variant2ClinVarID: 11909

Variant2CAID: CA204563

AdditionalVariants: N/A

ParentalGenotype: N/A

PreviouslyPublished N/A

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

DiseaseAssertion: MPSI-H

FamilyInfo: N/A

CasePresentingHPOs: Corneal clouding (HP:0007957)

CaseHPOFreeText: N/A

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

CaseNotHPOFreeText: N/A

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

CaseUrineGAGs: 0.38 DS/CS

CaseERT: Yes

CaseBMT: Yes, Cord

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

Variant1ClinVarID: 11908

Variant1CAID: CA220498

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

Variant2ClinVarID: 11909

Variant2CAID: CA204563

AdditionalVariants: N/A

ParentalGenotype: N/A

PreviouslyPublished N/A

Case#: Patient 6, born in 2003 (paper published in 2017), 1 year (age at first treatment), 20 months (age at last 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: 31 ng/mol (31 weight matched enzyme reference assay)

CaseUrineGAGs: 0.39 DS/CS

CaseERT: Yes

CaseBMT: Yes, MUD

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

Variant1ClinVarID: 11909

Variant1CAID: CA204563

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

Variant2ClinVarID: 11909

Variant2CAID: CA204563

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 23, Italy

DiseaseAssertion: MPS1-H

FamilyInfo: N/A

CasePresentingHPOs: N/A

CaseHPOFreeText: N/A

CaseNotHPOs: N/A

CaseNotHPOFreeText: N/A

CaseEnzymeAssay: N/A

CaseUrineGAGs: N/A

CaseERT: N/A

CaseBMT: N/A

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

Variant1ClinVarID: 11909

Variant1CAID: CA204563

Variant2: c.1487C>G (p.P496R)

Variant2ClinVarID: 496861

Variant2CAID: CA2802275

AdditionalVariants: N/A

ParentalGenotype: N/A

PreviouslyPublished N/A

Case#: Patient 44, Poland

DiseaseAssertion: MPS1-S

FamilyInfo: N/A

CasePresentingHPOs: N/A

CaseHPOFreeText: N/A

CaseNotHPOs: N/A

CaseNotHPOFreeText: N/A

CaseEnzymeAssay: N/A

CaseUrineGAGs: N/A

CaseERT: N/A

CaseBMT: N/A

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

Variant1ClinVarID: 11909

Variant1CAID: CA204563

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

Variant2ClinVarID: 638074

Variant2CAID: CA2802098

AdditionalVariants: N/A

ParentalGenotype: N/A

PreviouslyPublished N/A

Case#: Patient 15, Italy

DiseaseAssertion: MPS1-S

FamilyInfo: N/A

CasePresentingHPOs: N/A

CaseHPOFreeText: N/A

CaseNotHPOs: N/A

CaseNotHPOFreeText: N/A

CaseEnzymeAssay: N/A

CaseUrineGAGs: N/A

CaseERT: N/A

CaseBMT: N/A

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

Variant1ClinVarID: 11909

Variant1CAID: CA204563

Variant2: c.1333_1335del (p.Asp445del)

Variant2ClinVarID: 840115

Variant2CAID: CA916082626

AdditionalVariants: N/A

ParentalGenotype: N/A

PreviouslyPublished N/A

Case#: Patient 17, Italy

DiseaseAssertion: MPS1-H

FamilyInfo: N/A

CasePresentingHPOs: N/A

CaseHPOFreeText: N/A

CaseNotHPOs: N/A

CaseNotHPOFreeText: N/A

CaseEnzymeAssay: N/A

CaseUrineGAGs: N/A

CaseERT: N/A

CaseBMT: N/A

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

Variant1ClinVarID: 11909

Variant1CAID: CA204563

Variant2: c.1487C>G (p.P496R)

Variant2ClinVarID: 496861

Variant2CAID: CA2802275

AdditionalVariants: N/A

ParentalGenotype: N/A

PreviouslyPublished N/A

Case#: Patient 30, Italy

DiseaseAssertion: MPS1-H

FamilyInfo: N/A

CasePresentingHPOs: N/A

CaseHPOFreeText: N/A

CaseNotHPOs: N/A

CaseNotHPOFreeText: N/A

CaseEnzymeAssay: N/A

CaseUrineGAGs: N/A

CaseERT: N/A

CaseBMT: N/A

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

Variant1ClinVarID: 11909

Variant1CAID: CA204563

Variant2: c.1487C>G (p.P496R)

Variant2ClinVarID: 496861

Variant2CAID: CA2802275

AdditionalVariants: N/A

ParentalGenotype: N/A

PreviouslyPublished N/A

Case#: Patient 33, Italy

DiseaseAssertion: MPS1-H

FamilyInfo: N/A

CasePresentingHPOs: N/A

CaseHPOFreeText: N/A

CaseNotHPOs: N/A

CaseNotHPOFreeText: N/A

CaseEnzymeAssay: N/A

CaseUrineGAGs: N/A

CaseERT: N/A

CaseBMT: N/A

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

Variant1ClinVarID: 11909

Variant1CAID: CA204563

Variant2: c.1487C>G (p.P496R)

Variant2ClinVarID: 496861

Variant2CAID: CA2802275

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 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 35, Italy

DiseaseAssertion: MPS1-H

FamilyInfo: N/A

CasePresentingHPOs: N/A

CaseHPOFreeText: N/A

CaseNotHPOs: N/A

CaseNotHPOFreeText: N/A

CaseEnzymeAssay: N/A

CaseUrineGAGs: N/A

CaseERT: N/A

CaseBMT: N/A

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

Variant1ClinVarID: 11909

Variant1CAID: CA204563

Variant2: c.398_403del (p.Met133_Gly134del)

Variant2ClinVarID: 863830

Variant2CAID: CA2801912

AdditionalVariants: N/A

ParentalGenotype: N/A

PreviouslyPublished N/A

Case#: Patient 26 (see Table 2), 40 weeks (Gestational age)

DiseaseAssertion: MPS1-S

FamilyInfo: Sibling of Patient 25 (see Table 2)

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.1148G>A (p.R383H)

Variant2ClinVarID: 558189

Variant2CAID: CA:2802205

AdditionalVariants: N/A

ParentalGenotype: N/A

PreviouslyPublished N/A

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

DiseaseAssertion: MPS1-H

FamilyInfo: N/A

CasePresentingHPOs: Inguinal hernia (HP:0000023)

CaseHPOFreeText: N/A

CaseNotHPOs: N/A

CaseNotHPOFreeText: Upper respiratory tract involvement

CaseEnzymeAssay: N/A

CaseUrineGAGs: N/A

CaseERT: N/A

CaseBMT: N/A

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

Variant1ClinVarID: 11908

Variant1CAID: CA220498

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

Variant2ClinVarID: 11909

Variant2CAID: CA204563

AdditionalVariants: N/A

ParentalGenotype: N/A

PreviouslyPublished N/A

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

DiseaseAssertion: MPS1-H

FamilyInfo: N/A

CasePresentingHPOs: N/A

CaseHPOFreeText: N/A

CaseNotHPOs: N/A

CaseNotHPOFreeText: N/A

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

CaseUrineGAGs: N/A

CaseERT: N/A

CaseBMT: N/A

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

Variant1ClinVarID: 11909

Variant1CAID: CA204563

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

Variant2ClinVarID: 222995

Variant2CAID: CA356986

AdditionalVariants: N/A

ParentalGenotype: N/A

PreviouslyPublished N/A

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

DiseaseAssertion: MPS1-H

FamilyInfo: N/A

CasePresentingHPOs: N/A

CaseHPOFreeText: Upper respiratory tract involvement

CaseNotHPOs: Inguinal hernia (HP:0000023)

CaseNotHPOFreeText: N/A

CaseEnzymeAssay: N/A

CaseUrineGAGs: N/A

CaseERT: N/A

CaseBMT: N/A

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

Variant1ClinVarID: 11909

Variant1CAID: CA204563

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

Variant2ClinVarID: 222995

Variant2CAID: CA:356986

AdditionalVariants: N/A

ParentalGenotype: N/A

PreviouslyPublished N/A

Case#: Patient 23 (see Table 2), 40 weeks (Gestational age)

DiseaseAssertion: MPS1-S

FamilyInfo: Sibling of Patient 26 (see Table 2)

CasePresentingHPOs: N/A

CaseHPOFreeText: N/A

CaseNotHPOs: N/A

CaseNotHPOFreeText: N/A

CaseEnzymeAssay: 1.17 nmol x mg-1 × hr-1

CaseUrineGAGs: N/A

CaseERT: N/A

CaseBMT: N/A

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

Variant1ClinVarID: 11909

Variant1CAID: CA204563

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

Variant2ClinVarID: 558189

Variant2CAID: CA:2802205

AdditionalVariants: N/A

ParentalGenotype: N/A

PreviouslyPublished N/A

Case#: Patient 6 (see Table 2), 33 weeks, 6 days (Gestational age)

DiseaseAssertion: MPS1-H

FamilyInfo: N/A

CasePresentingHPOs: N/A

CaseHPOFreeText: N/A

CaseNotHPOs: N/A

CaseNotHPOFreeText: N/A

CaseEnzymeAssay: 0.47 nmol x mg-1 × hr-1

CaseUrineGAGs: N/A

CaseERT:N/A

CaseBMT: N/A

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

Variant1ClinVarID: 11909

Variant1CAID: CA204563

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

Variant2ClinVarID: 222995

Variant2CAID: CA356986

AdditionalVariants: N/A

ParentalGenotype: N/A

PreviouslyPublished N/A

Case#: Patient 8 (see Table 2), 38 weeks (Gestational age)

DiseaseAssertion: MPS1-H

FamilyInfo: N/A

CasePresentingHPOs: N/A

CaseHPOFreeText: Upper respiratory tract involvement

CaseNotHPOs: N/A

CaseNotHPOFreeText: N/A

CaseEnzymeAssay: 0.58 nmol x mg-1 × hr-1

CaseUrineGAGs: N/A

CaseERT: N/A

CaseBMT: N/A

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

Variant1ClinVarID: 11909

Variant1CAID: CA204563

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

Variant2ClinVarID: 222995

Variant2CAID: CA356986

AdditionalVariants: N/A

ParentalGenotype: N/A

PreviouslyPublished N/A

Case#: Patient 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 4, female, 10.9 months (age at diagnosis), 16.5 months (age at HSCT), 8.3 - 17.3 months (age at ERT), 7 MRI + neuropsychological observations over the course of 11 years.

DiseaseAssertion: MPS-1H

FamilyInfo: N/A

CasePresentingHPOs: N/A

CaseHPOFreeText: N/A

CaseNotHPOs: N/A

CaseNotHPOFreeText: N/A

CaseEnzymeAssay: 67.7 nmol/h/mg (Normal values: 11-43 nmol/h/mg)

CaseUrineGAGs: N/A

CaseERT: Yes

CaseBMT: Yes

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

Variant1ClinVarID: 11909

Variant1CAID: CA204563

Variant2: c.1487C>G (p.P496R)

Variant2ClinVarID: 496861

Variant2CAID: CA2802275

AdditionalVariants: N/A

ParentalGenotype: N/A

PreviouslyPublished N/A

Case#: Patient 6, female, 8.3 months (age at diagnosis), 12.4 months (age at HSCT), 9.0 - 14.7 months (age at ERT), 5 MRI + neuropsychological observations over the course of 10 years.

DiseaseAssertion: MPS-1H

FamilyInfo: N/A

CasePresentingHPOs: N/A

CaseHPOFreeText: N/A

CaseNotHPOs: N/A

CaseNotHPOFreeText: N/A

CaseEnzymeAssay: 32.7 nmol/h/mg (Normal values: 11-43 nmol/h/mg)

CaseUrineGAGs: N/A

CaseERT: Yes

CaseBMT: Yes, transplanted with an unrelated cord blood unit.

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

Variant1ClinVarID: 11909

Variant1CAID: CA204563

Variant2: c.1487C>G (p.P496R)

Variant2ClinVarID: 496861

Variant2CAID: CA2802275

AdditionalVariants: N/A

ParentalGenotype: N/A

PreviouslyPublished N/A

Case#: Patient 4, female, 8.3 months (age at HSCT), 4.5 months (age at ERT).

DiseaseAssertion: MPS1-H

FamilyInfo: N/A

CasePresentingHPOs:

CaseHPOFreeText: Cy-induced acute cardiomyopathy

CaseNotHPOs: N/A

CaseNotHPOFreeText: N/A

CaseEnzymeAssay: 0.31 (at diagnosis), 15.7 (after HSCT) Units not provided.

CaseUrineGAGs: N/A

CaseERT: Yes - 114 days duration

CaseBMT: Yes - MUD (matched unrelated donor) with stem cells sourcing from the BM (bone marrow).

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

Variant1ClinVarID: 11909

Variant1CAID: CA204563

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

Variant2ClinVarID: 11908

Variant2CAID: CA220498

AdditionalVariants: N/A

ParentalGenotype: N/A

PreviouslyPublished N/A

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

DiseaseAssertion: MPS1-H

FamilyInfo: N/A

CasePresentingHPOs: Pneumonia (HP:0002090)

CaseHPOFreeText: Adenovirus, gastrointestinal and skin (GVHD)

CaseNotHPOs: N/A

CaseNotHPOFreeText: N/A

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

CaseUrineGAGs: N/A

CaseERT: Yes - 87 days duration

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

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

Variant1ClinVarID: 11909

Variant1CAID: CA204563

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

Variant2ClinVarID: 11908

Variant2CAID: CA220498

AdditionalVariants: N/A

ParentalGenotype: N/A

PreviouslyPublished N/A

Case#: Patient 3, 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: 0.05 nmol/mg/h (reference range 135 ± 57 nmol/mg/h)

CaseUrineGAGs: 265.24 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.208C>T (p.Q70X)

Variant2ClinVarID: 11909

Variant2CAID: CA204563

AdditionalVariants: N/A

ParentalGenotype: N/A

PreviouslyPublished N/A

Case#: Patient 1, male, Russian

DiseaseAssertion: MPS1-H

FamilyInfo: N/A

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

CaseHPOFreeText: N/A

CaseNotHPOs: N/A

CaseNotHPOFreeText: N/A

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

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

CaseERT: No

CaseBMT: No

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

Variant1ClinVarID: 11909

Variant1CAID: CA204563

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

Variant2ClinVarID: 550382

Variant2CAID: CA2802114

AdditionalVariants: N/A

ParentalGenotype: N/A

PreviouslyPublished N/A

Case#: Patient 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#: Patient 2

DiseaseAssertion: MPS1-H

FamilyInfo: N/A

CasePresentingHPOs: N/A

CaseHPOFreeText: N/A

CaseNotHPOs: N/A

CaseNotHPOFreeText: N/A

CaseEnzymeAssay: N/A

CaseUrineGAGs: N/A

CaseERT: N/A

CaseBMT: N/A

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

Variant1ClinVarID: 11909

Variant1CAID: CA204563

Variant2: c.398_403del (p.Met133_Gly134del)

Variant2ClinVarID: 863830

Variant2CAID: CA2801912

AdditionalVariants: N/A

ParentalGenotype: N/A

PreviouslyPublished N/A

Case#: Patient 3

DiseaseAssertion: MPS1

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.1487C>G (p.P496R)

Variant2ClinVarID: 496861

Variant2CAID: CA2802275

AdditionalVariants: N/A

ParentalGenotype: N/A

PreviouslyPublished N/A

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

DiseaseAssertion: Hurler Syndrome

FamilyInfo: Not Provided

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

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

CaseNotHPOs: N/A

CaseNotHPOFreeText: N/A

CaseEnzymeAssay: N/A

CaseUrineGAGs: N/A

CaseERT: N/A

CaseBMT: N/A

GenotypingMethod: Not Provided

Variant1: p.Q70X

Variant1ClinVarID: 11909

Variant1CAID: CA204563

Variant2: p.W626X

Variant2ClinVarID: 928997

Variant2CAID: CA355965968

AdditionalVariants: p.Q33H/Q33H, p.L118

ParentalGenotype: N/A

PreviouslyPublished N/A

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

DiseaseAssertion: Hurler Syndrome

FamilyInfo: Not Provided

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

CaseHPOFreeText: Mental Development (Delayed)

CaseNotHPOs: N/A

CaseNotHPOFreeText: N/A

CaseEnzymeAssay: N/A

CaseUrineGAGs: N/A

CaseERT: N/A

CaseBMT: N/A

GenotypingMethod: Not Provided

Variant1: p.Q70X

Variant1ClinVarID: 11909

Variant1CAID: CA204563

Variant2: p.D315Y

Variant2ClinVarID: N/A

Variant2CAID: CA355962740

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

ParentalGenotype: N/A

PreviouslyPublished N/A

Case#: 13, Female, Infancy (onset), 1,5 years (diagnosed), 5 years (report)

DiseaseAssertion: Hurler Syndrome

FamilyInfo: Not Provided

CasePresentingHPOs: HP:0001387, HP:0002240, HP:0001744, HP:0012185, HP:0000280, HP:0000943, HP:0007957 (Joint Stiffness, Hepatomegaly, Splenomegaly, Carpal Tunnel Syndrome, Coarse Facial Features, Dysostosis Multiplex, Corneal Clouding)

CaseHPOFreeText: Mental Development (Delayed)

CaseNotHPOs: N/A

CaseNotHPOFreeText: N/A

CaseEnzymeAssay: N/A

CaseUrineGAGs: N/A

CaseERT: N/A

CaseBMT: N/A

GenotypingMethod: Not Provided

Variant1: p.Q70X

Variant1ClinVarID: 11909

Variant1CAID: CA204563

Variant2: c.1650+5G>A (splicing error)

Variant2ClinVarID: 92634

Variant2CAID: CA220504

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

ParentalGenotype: N/A

PreviouslyPublished N/A

Case#: 15, Female, Infancy (onset), 10 months (diagnosed), 12 years (report)

DiseaseAssertion: Hurler-Scheie Syndrome

FamilyInfo: Not Provided

CasePresentingHPOs: HP:0004322, HP:0000256, HP:0001387, HP:0002240, HP:0001744, HP:0000023, HP:0000158, HP:0000280, HP:0000943, HP:0007957 (Short Stature, Macrocephaly, Joint Stiffness, Hepatomegaly (moderate), Splenomegaly (moderate), Inguinal Hernia, Large Tongue, Coarse Facial Features, Dysostosis Multiplex, Corneal Clouding)

CaseHPOFreeText: (Mental Development (Delayed), Systolic murmur 3-4/6, After ERT: decreased illness (obstructive bronchitis), decreased organomegaly, increased mobility)

CaseNotHPOs: N/A

CaseNotHPOFreeText: N/A

CaseEnzymeAssay: N/A

CaseUrineGAGs: Decreased excretion of GAGs in the urine

CaseERT: Had an ERT

CaseBMT: N/A

GenotypingMethod: Not Provided

Variant1: p.Q70X

Variant1ClinVarID: 11909

Variant1CAID: CA204563

Variant2: p.R628X

Variant2ClinVarID: 550421

Variant2CAID: CA2802462

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

ParentalGenotype: N/A

PreviouslyPublished N/A

Case#: 10, Male, 2 months (onset), 2 months (diagnosed), 2 months (report), deceased (due to severe graft versus host disease)

DiseaseAssertion: Hurler Syndrome

FamilyInfo: Not Provided

CasePresentingHPOs: HP:0002240, HP:0001744, HP:0001537, HP:0000158, HP:0000280, HP:0000943, HP:0007957 (Hepatomegaly (moderate), Splenomegaly (moderate), Umbilical Hernia, Large Tongue, Coarse Facial Features, Dysostosis Multiplex, Corneal Clouding)

CaseHPOFreeText: Mental Development (Delayed since early infancy)

CaseNotHPOs: HP:0000256 (Macrocephaly)

CaseNotHPOFreeText: N/A

CaseEnzymeAssay: N/A

CaseUrineGAGs: N/A

CaseERT: N/A

CaseBMT: Hematopoietic Stem Cell Transplantation at 5m

GenotypingMethod: Not Provided

Variant1: p.Q70X

Variant1ClinVarID: 11909

Variant1CAID: CA204563

Variant2: p.Q70X

Variant2ClinVarID: 11909

Variant2CAID: CA204563

AdditionalVariants: p.Q33H/Q33H, p.L118/L118

ParentalGenotype: N/A

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#: MPS 1 patient

DiseaseAssertion: N/A

FamilyInfo: N/A

CasePresentingHPOs: N/A

CaseHPOFreeText: N/A

CaseNotHPOs: N/A

CaseNotHPOFreeText: N/A

CaseEnzymeAssay: N/A

CaseUrineGAGs: N/A

CaseERT: N/A

CaseBMT: N/A

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

Variant1ClinVarID: 11909

Variant1CAID: CA204563

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

Variant2ClinVarID: 4539822

Variant2CAID: CA355962740

AdditionalVariants: N/A

ParentalGenotype: N/A

PreviouslyPublished N/A

Case#: 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.1877G>A (p.W626X)

Variant2ClinVarID: 928997

Variant2CAID: CA355965968

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.501C>G (p.Y167X)

Variant2ClinVarID: 92644

Variant2CAID: CA220511

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 Sample unique ID 3, 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:Severe MPS1, Hurler Syndrome

FamilyInfo:None

CasePresentingHPOs: HP:0007957 (mild corneal clouding), HP:0011729 (decreased joint range of motion), HP:0008454 (lumbar kyphosis)

CaseHPOFreeText: A history of multiple failed hearing tests, chronic serous otitis media, and pressure equalizer tube placement

CaseNotHPOs:None

CaseNotHPOFreeText: None

CaseEnzymeAssay: IDUA activity 0.163 (2.3) umol/L/h (%DMA) through dried blood spot during newborn screening and 4.3 pmol/punch/h Confirmatory IDUA enzyme

CaseUrineGAGs: DS 128.4 g/mol creatinine and HS 466.6 g/mol creatinine

CaseERT:No

CaseBMT: The patient received a cord blood transplantation at 7 months of age.

Variant1:1 homozygous pathogenic: c.208C>T; p.Q70* (∗ IDUA enzyme activity reference range is < 8.0 pmol/punch/hour.)

Variant1ClinVarID: 11909

Variant1CAID: CA204563

Variant2:1 homozygous pathogenic: c.208C>T; p.Q70* (∗ IDUA enzyme activity reference range is < 8.0 pmol/punch/hour.)

Variant2ClinVarID: 11909

Variant2CAID: CA204563

AdditionalVariants:N/A

ParentalGenotype:N/A

PreviouslyPublished:N/A

Case#: Patient No. 3 (Table 1), White race, female, 1.95 years old (age at time of gene therapy), 75 IQ score, 2.13 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.208C>T (p.Q70X)

Variant1ClinVarID: 11909

Variant1CAID: CA204563

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

Variant2ClinVarID: 11909

Variant2CAID: CA204563

AdditionalVariants: N/A

ParentalGenotype: N/A

PreviouslyPublished N/A

Case#: Patient No. 4 (Table 1), White race, male, 1.21 years old (age at time of gene therapy), 95 IQ score, 2.07 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.208C>T (p.Q70X)

Variant1ClinVarID: 11909

Variant1CAID: CA204563

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

Variant2ClinVarID: 11909

Variant2CAID: CA204563

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

CaseUrineGAGs: N/A

CaseERT: N/A

CaseBMT: N/A

Variant1: c.1898C>A (p.S633X)

Variant1ClinVarID: 1068474

Variant1CAID: CA355966009

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

Variant2ClinVarID: 11909

Variant2CAID: CA204563

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

CaseUrineGAGs: N/A

CaseERT: N/A

CaseBMT: N/A

Variant1: c.1278_1284dupCCCCCAG (p.G429PfsTer82)

Variant1ClinVarID: N/A

Variant1CAID: CA645372299

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

Variant2ClinVarID: 11909

Variant2CAID: CA204563

AdditionalVariants: N/A

ParentalGenotype: N/A

PreviouslyPublished N/A

Case#: Patient 1, male, 15 months (age at diagnosis), 20.5 months (age at HSCT), weight of 12.7 kg (at HSCT), 5.8 years (age at report). Upon HSCT the patient made neurodevelopmental progress and attended kindergarten, he still had severe mental disabilities and aggressive behavior problems.

DiseaseAssertion: MPS1-H

FamilyInfo: N/A

CasePresentingHPOs: Neurodevelopmental delay, speech delay, mild lumbar hyperlordosis (HP:0012758, HP:0000750, HP:0002938)

CaseHPOFreeText: N/A

CaseNotHPOs: N/A

CaseNotHPOFreeText: N/A

CaseEnzymeAssay: Activity of alpha-L-iduronidase in leukocytes was normal from 2 months after cessation of ERT.

CaseUrineGAGs: Patient had normal excretion of total urine GAGs.

CaseERT: Yes - 21 weeks of ERT before HSCT. Continued until day 107 of HSCT.

CaseBMT: Yes - interval diagnosis for HSCT (22 weeks). The donor was female and unrelated.

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

Variant1ClinVarID: 11909

Variant1CAID: CA204563

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

Variant2ClinVarID: 11908

Variant2CAID: CA220498

AdditionalVariants: N/A

ParentalGenotype: N/A

PreviouslyPublished N/A

Case#: Patient 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#: Patient 11, male, age of diagnosis is 11 months

DiseaseAssertion: Mucopolysaccharidosis type I, MPS-I, Maternal Mucopolysaccharidosis type I

FamilyInfo: No family information provided in this paper

CasePresentingHPOs:

CaseHPOFreeText:

CaseNotHPOs:

CaseNotHPOFreeText:

CaseEnzymeAssay: No results of iduronidase enzyme assay mentioned in this paper

CaseUrineGAGs: No record/details of urine GAG levels in this paper

CaseERT: Don't know

CaseBMT: Don't know

Variant1: c.208 C>T (p.Gln70*)

Variant1ClinVarID: 11909

Variant1CAID: CA204563

Variant2: c.208 C>T (p.Gln70*)

Variant2ClinVarID: 11909

Variant2CAID: CA204563

AdditionalVariants: No additional variants mentioned in this paper

ParentalGenotype: Variant of proband is from his mother; "11-month-old boy with a homozygous nonsense variant, c.208C>T (p.Gln70*), in exon 2 of IDUA, resulting from UPD(4)mat of 18 Mb on chromosome 4 pter."

PreviouslyPublished: Author states that he found this patient from 30737479 (PMID).

Case#: Patient A, male, 11 months (age of diagnosis), at 12 years of age (age at report) he has cognitive status of 8 years.

DiseaseAssertion: MPS1-Hurler

FamilyInfo: Mother and father were tested - see maternal genotype below.

CasePresentingHPOs: N/A

CaseHPOFreeText: Splenectomy procedure conducted

CaseNotHPOs: N/A

CaseNotHPOFreeText: N/A

CaseEnzymeAssay: α-L-iduronidase showed a profound deficiency (0.2 nmoles/17 h/mg, with a normal range of 25–90)

CaseUrineGAGs: N/A

CaseERT: Yes starting at 13 months

CaseBMT: Yes received an allogenic stem cell transplant at 1 year and 4 months.

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

Variant1ClinVarID: 11909

Variant1CAID: CA204563

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

Variant2ClinVarID: 11909

Variant2CAID: CA204563

AdditionalVariants: N/A

ParentalGenotype: Mother was heterozygous for c.208C>T while father was negative.

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: Abnormal

CaseUrineGAGs: Abnormal

CaseERT: N/A

CaseBMT: N/A

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

Variant1ClinVarID: 11909

Variant1CAID: CA204563

Variant2: c.1269C>A (p.S423R)

Variant2ClinVarID: 856833

Variant2CAID: CA91169964

AdditionalVariants: N/A

ParentalGenotype: N/A

PreviouslyPublished N/A

Case#: Patient A

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.1651-1G>T

Variant2ClinVarID: N/A

Variant2CAID: CA355965149

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 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#: 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

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#: 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

Case#: Three patients are from The Netherlands

DiseaseAssertion: MPSI-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.653T>C (p.L218P)

Variant1ClinVarID: 222995

Variant1CAID: CA356986

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

Variant2ClinVarID: 11909

Variant2CAID: CA204563

AdditionalVariants: N/A

ParentalGenotype: N/A

PreviouslyPublished N/A

Case#: Three patients are from The Netherlands

DiseaseAssertion: MPSI-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.653T>C (p.L218P)

Variant1ClinVarID: 222995

Variant1CAID: CA356986

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

Variant2ClinVarID: 11909

Variant2CAID: CA204563

AdditionalVariants: N/A

ParentalGenotype: N/A

PreviouslyPublished N/A

Case#: Three patients are from The Netherlands

DiseaseAssertion: MPSI-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.653T>C (p.L218P)

Variant1ClinVarID: 222995

Variant1CAID: CA356986

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

Variant2ClinVarID: 11909

Variant2CAID: CA204563

AdditionalVariants: N/A

ParentalGenotype: N/A

PreviouslyPublished N/A

Case#: 22-month-old Norwegian female patient

DiseaseAssertion: MPS-H

FamilyInfo: Mother and father received parental testing.

CasePresentingHPOs: Joint stiffness (HP:0001387)

CaseHPOFreeText: She had a tendency to fall without normal protective reactions. Typical facial appearance and other clinical findings were suggestive of MPS I Hurler, and this diagnosis was also supported by X-ray images which showed characteristic skeletal changes. Motor development appeared slightly delayed, while intellectual development was considered to be normal.

CaseNotHPOs: Corneal clouding (HP:0007957)

CaseNotHPOFreeText: N/A

CaseEnzymeAssay: 0.006 μmol phenol/18 h/mg protein. Normal range of IDUA activity (n = 52, healthy volunteers): 0.143–0.351 μmol phenol/18 h/mg protein.

CaseUrineGAGs: Urinary GAG excretion - 101 mg GAG/mmol creatinine. The patient demonstrated increased excretion of GAGs, which were identified as HS and DS. Normal age adjusted range of urinary GAG excretion: 14–34 mg GAG/mmol creatinine.

CaseERT: The patient was initiated on enzyme replacement therapy (ERT) with weekly infusions of recombinant α-l-iduronidase 100 IE/kg

CaseBMT: The patient successfully received hematopoietic stem cell transplantation (HSCT) 4 months after ERT.

Variant1: c.1727+3G>C

Variant1ClinVarID: 4817926

Variant1CAID: CA91171181

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

Variant2ClinVarID: 11909

Variant2CAID: CA204563

AdditionalVariants: N/A

ParentalGenotype: Mother: c.208C>T (p.Q70X); 0.071 μmol phenol/18 h/mg protein (IDUA activity). Father: c.1727+3G>C; 0.079 μmol phenol/18 h/mg protein (IDUA activity).

PreviouslyPublished N/A