Case#: MPS I_Case 02, female newborn

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

FamilyInfo: MPS I_Case 02 and MPS I_Case 03 are twins

CasePresentingHPOs:

CaseHPOFreeText:

CaseNotHPOs:

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

CaseEnzymeAssay: Proband identified by newborn screening. alpha-L-iduronidase activity in dried blood spot sample is 0.59 umole/L/Hr; this is below the study's DBS enzyme activity cutoff value of 3 umol/L/h

CaseUrineGAGs: Urine DMB GAG ratio is 204.7mg/mmol creatinine. 99.60 ug/ml dermatan sulfate in urine (<0.41 ug/ml is the reference cutoff for dermatan sulfate in this study). 13.31 ug/ml heparan sulfate in urine (<0.8 ug/ml is the reference cutoff for heparan sulfate in this study). 0.83 ug/ml keratan sulfate in urine.

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

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

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

Variant1ClinVarID: 11927

Variant1CAID: CA256128

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

Variant2ClinVarID: 11925

Variant2CAID: CA256126

AdditionalVariants: No additional variants mentioned

ParentalGenotype: No parental testing results are available

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

Case#: MPS I_Case 03, female newborn

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

FamilyInfo: MPS I_Case 03 and MPS I_Case 02 are twins

CasePresentingHPOs:

CaseHPOFreeText:

CaseNotHPOs:

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

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

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

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

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

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

Variant1ClinVarID: 11927

Variant1CAID: CA256128

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

Variant2ClinVarID: 11925

Variant2CAID: CA256126

AdditionalVariants: No additional variants mentioned

ParentalGenotype: No parental testing results are available

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

Case#: 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: T364M

Variant1ClinVarID: 11925

Variant1CAID: CA256126

Variant2: N/A

Variant2ClinVarID: N/A

Variant2CAID: N/A

AdditionalVariants: N/A

ParentalGenotype: N/A

PreviouslyPublished: N/A

Case#: Patient 55, 6 months old (age at report), female, Indian

DiseaseAssertion: MPS1-H

FamilyInfo: N/A

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

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.589G>A (p.Gly197Ser)

Variant1ClinVarID: 1526094

Variant1CAID: CA355961839

Variant2: c.1091C>T (p.Thr364Met)

Variant2ClinVarID: 11925

Variant2CAID: CA256126

AdditionalVariants: N/A

ParentalGenotype: N/A

PreviouslyPublished N/A

Case#: Infant #10, female.

DiseaseAssertion: MPS-I

FamilyInfo: N/A

CasePresentingHPOs: N/A

CaseHPOFreeText: N/A

CaseNotHPOs: N/A

CaseNotHPOFreeText: N/A

CaseEnzymeAssay: 0.70 IDUA enzyme activity (Ref. 5.9–27.8 μmol/g protein/h)

CaseUrineGAGs: DMB/Cre. Ratio - 204.70, DS - 176.96, HS - 28.51, KS - 1.78 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.1037T>G (p.L346R)

Variant1ClinVarID: 11927

Variant1CAID: CA256128

Variant2: c.1091C>T (p.T364M) Article has (p.364M) which appears to be a typo.

Variant2ClinVarID: 11925

Variant2CAID: CA256126

AdditionalVariants: N/A

ParentalGenotype: N/A

PreviouslyPublished N/A

Case#: Infant #11, female.

DiseaseAssertion: MPS-I

FamilyInfo: N/A

CasePresentingHPOs: N/A

CaseHPOFreeText: N/A

CaseNotHPOs: N/A

CaseNotHPOFreeText: N/A

CaseEnzymeAssay: 0.80 IDUA enzyme activity (Ref. 5.9–27.8 μmol/g protein/h)

CaseUrineGAGs: DMB/Cre. Ratio - 239.25, DS - 296.10, HS - 33.55, KS - 1.37 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.1037T>G (p.L346R)

Variant1ClinVarID: 11927

Variant1CAID: CA256128

Variant2: c.1091C>T (p.T364M) Article has (p.364M) which appears to be a typo.

Variant2ClinVarID: 11925

Variant2CAID: CA256126

AdditionalVariants: N/A

ParentalGenotype: N/A

PreviouslyPublished N/A

Case#: Patient 6, female, twin of Patient 5 (see Table 1)

DiseaseAssertion: MPS I

FamilyInfo: N/A

CasePresentingHPOs: N/A

CaseHPOFreeText: N/A

CaseNotHPOs: N/A

CaseNotHPOFreeText: N/A

CaseEnzymeAssay: Low IDUA enzyme activity 0.75 (Ref. 4.87 ~ 54.70 μmol/g protein/h)

CaseUrineGAGs: Positive GAG tests

CaseERT: N/A

CaseBMT: N/A

Variant1: c.1037T>G (p.L346R)

Variant1ClinVarID: 11927

Variant1CAID: CA256128

Variant2: c.1091C>T (p.T364M)

Variant2ClinVarID: 11925

Variant2CAID: CA256126

AdditionalVariants: N/A

ParentalGenotype: N/A

PreviouslyPublished N/A

Case#: Patient 5, female, twin of Patient 6 (see Table 1)

DiseaseAssertion: MPS I

FamilyInfo: N/A

CasePresentingHPOs: N/A

CaseHPOFreeText: N/A

CaseNotHPOs: N/A

CaseNotHPOFreeText: N/A

CaseEnzymeAssay: Low IDUA enzyme activity 0.81 (Ref. 4.87 ~ 54.70 μmol/g protein/h)

CaseUrineGAGs: Positive GAG tests

CaseERT: N/A

CaseBMT: N/A

Variant1: c.1037T>G (p.L346R)

Variant1ClinVarID: 11927

Variant1CAID: CA256128

Variant2: c.1091C>T (p.T364M)

Variant2ClinVarID: 11925

Variant2CAID: CA256126

AdditionalVariants: N/A

ParentalGenotype: N/A

PreviouslyPublished N/A

Case#: TW1-2 ID number, Table S1.1 of Supplementary Material. Female, 1-2 years old (age at first symptoms), 3 years and 2 months old (age at diagnosis). Stored Frozen (-20ºC).

DiseaseAssertion: Severe MPS-I

FamilyInfo: Twin of patient TW1-3.

CasePresentingHPOs: N/A

CaseHPOFreeText: N/A

CaseNotHPOs: N/A

CaseNotHPOFreeText: N/A

CaseEnzymeAssay: N/A

CaseUrineGAGs: 615 fmol/punch

CaseERT: N/A

CaseBMT: N/A

Variant1: c.1037T>G (p.L346R)

Variant1ClinVarID: 11927

Variant1CAID: CA256128

Variant2: c.1091C>T (p.T364M)

Variant2ClinVarID: 11925

Variant2CAID: CA256126

AdditionalVariants: N/A

ParentalGenotype: N/A

PreviouslyPublished N/A

Case#: TW1-3 ID number, Table S1.1 of Supplementary Material. Female, 1-2 years old (age at first symptoms), 1 year and 6 months old (age at diagnosis). Stored Frozen (-20ºC)

DiseaseAssertion: Severe MPS-I

FamilyInfo: Twin of patient TW1-2.

CasePresentingHPOs: N/A

CaseHPOFreeText: N/A

CaseNotHPOs: N/A

CaseNotHPOFreeText: N/A

CaseEnzymeAssay: N/A

CaseUrineGAGs: 589 fmol/punch

CaseERT: N/A

CaseBMT: N/A

Variant1: c.1037T>G (p.L346R)

Variant1ClinVarID: 11927

Variant1CAID: CA256128

Variant2: c.1091C>T (p.T364M)

Variant2ClinVarID: 11925

Variant2CAID: CA256126

AdditionalVariants: N/A

ParentalGenotype: N/A

PreviouslyPublished N/A

Case#: Patient W2, 10 years old, Chinese. The patient had normal intelligence based on their performance in school.

DiseaseAssertion: MPS1-H/S

FamilyInfo: Maternal and paternal DNA were interpreted.

CasePresentingHPOs: Short stature, coarse facial features, severe skeletal deformities (HP:0004322, HP:0000280, HP:0000924)

CaseHPOFreeText: N/A

CaseNotHPOs: N/A

CaseNotHPOFreeText: N/A

CaseEnzymeAssay: N/A

CaseUrineGAGs: N/A

CaseERT: N/A

CaseBMT: N/A

Variant1: c.1091C>T (p.T364M)

Variant1ClinVarID: 11925

Variant1CAID: CA256126

Variant2: c.1091C>T (p.T364M)

Variant2ClinVarID: 11925

Variant2CAID: CA256126

AdditionalVariants: N/A

ParentalGenotype: N/A

PreviouslyPublished N/A