Case#: Patient F, female, 25 years old (age at report), 61 kg of weight (50th percentile), height of 154 cm (10th percentile). She is now working as an office secretary and also practices aerobic activity three times a week. She drives a car autonomously with her driving license which is renewed every 2 years. Her quality of life was measured with EQ-5D-Y and resulted good (100/100). Overall cognitive abilities are in the lower average expected for age (IQ:80), with difficulties in executive functioning, working memory, and arithmetic reasoning.

DiseaseAssertion: attenuated form of MPS-1

FamilyInfo: Affected younger sibling (Patient M), born to non-consanguineous Italian parents.

CasePresentingHPOs: Moderate facial coarseness, moderately severe dysostosis multiplex, scoliosis, hyperlordosis, genua valga, corneal clouding, hyperopia, astigmatism, otitis media (completely corrected by eyeglasses), hearing impairment, mild obstructive sleep apnea (since 16 years old), mild thickened skin (HP:0000280, HP:0000943, HP:0002650, HP:0003307, HP:0002857, HP:0007957, HP:0000540, HP:0000483, HP:0000388, HP:0000365, HP:0010535, HP:0001072)

CaseHPOFreeText: Liver and spleen volumes were normalized within the first year of ERT and remained within normal limits at clinical examination, claw feet, stiffness of the tibio-tarsal joint, ROM of hip and knees were within the normal ranges, improved stiffness of the trunk, movements of shoulders, elbows and wrists were within the normal range, limited flexion of fingers due to mild rigidity, normal cerebral MRI, a mild–moderate tricuspid insufficiency with pulmonary artery pressure (PAP) within the upper normal range (25 mmHG) was reported (at 16 years old), cardiac involvement.

CaseNotHPOs: N/A

CaseNotHPOFreeText: N/A

CaseEnzymeAssay: N/A

CaseUrineGAGs: Total urinary GAG excretion was slightly above the upper limit of the normal range (47 μg/mg creatinine with normal values < 26) with the qualitative assay showing a band of DS.

CaseERT: Yes - Began ERT and 5 years old. Laronidase infusions were started delivering weekly (at the dose of 0.5 mg/kg) using implanted venous access devices. Laronidase infusion generally lasted approximately 4 h, without the need for any premedication.

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 Yes (PMID: 20026495) and (PMID:26965916)

Case#: Patient M, male, 19 years of age (age at report), 71 kg of weight (50th percentile), height of 171 cm (25th percentile). He attended the last year of high school Institute of Art and practices aerobic activity three times a week. He is intellectually normal (IQ: 108) with a good quality of life (100/100 assessed by EQ-5D-Y).

DiseaseAssertion: attenuated form of MPS 1

FamilyInfo: Affected older sibling (Patient F), born to non-consanguineous Italian parents.

CasePresentingHPOs: Mild facial coarseness, temporomandibular joint dislocation, hypoplasia of the odontoid process, severe worsening of corneal clouding (noted at 12 months), mild hyperopia (noted at 7 years), astigmatism (noted at 7 years but completely corrected by eyeglasses), minimal multiplex dysostosis, mild joint stiffness, kyphosis, initial signs of carpal tunnel syndrome (HP:0000280, HP:6000814, HP:0003311, HP:0007957, HP:0000540, HP:0000483, HP:0000943, HP:0001387, HP:0002808, HP:0012185)

CaseHPOFreeText: Mild shoulder stiffness was present with limited forward elevation up to 120° and in abduction up to 100°, mild scoliosis with Cobb angle of 17°, triangular shape of cervical and thoracic vertebres (C4, C5, C6, D6, and D7), several dorsal herniated discs, normal brain MRI, mild heart involvement, stabilization of the cardiac valvulopathy, normal hearing.

CaseNotHPOs: Hepatosplenomegaly (HP:0001433)

CaseNotHPOFreeText: Respiratory or sleep disturbances, no recurrent infections.

CaseEnzymeAssay: N/A

CaseUrineGAGs: Total urinary glycosaminoglycans (GAG) determination on samples collected just before infusion remained within normal ranges (20,8 μg/mg creatinine with normal values < 42) but at the qualitative assay was present a band of DS.

CaseERT: Yes - Began ERT at 5 months old (pre symptomatically). Laronidase infusions were started delivering weekly (at the dose of 0.5 mg/kg) using implanted venous access devices. Laronidase infusion generally lasted approximately 4 h, without the need for any premedication.

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 Yes (PMID: 20026495) and (PMID:26965916)

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