Case#: Sibling 2, Patient F, female, 17 years old (age at report)

DiseaseAssertion: MPS1

FamilyInfo: Affected younger sibling (Sibling 1)

CasePresentingHPOs: HP:0000280, HP:0034337, HP:0001376, HP:0007957, HP:0000540, HP:0000483, HP:0000388, HP:0008513, HP:0000943, HP:0006536 (Coarse facial features, claw hand deformity, limitation of joint mobility, corneal clouding (unchanged since ERT), hyperopia (age 11), astigmatism (age 11), otitis media, mild bilateral conductive hearing (age 16), multiplex dysostosis, airway obstruction)

CaseHPOFreeText: Joint disease with limitation of range of motion of both proximal and distal joints, straight spine, cannot raise arms above head, median nerve compression, bilateral elongation of the Achilles tendon.

CaseNotHPOs: N/A

CaseNotHPOFreeText: Respiratory or sleep disturbances, no significant progression of previously reported moderate mitral insufficiency with thickened valve leaflets, anterior edge prolapse and mild left atrium thickening, no improvement of her moderately severe dysostosis multiplex with evidence of slight worsening of thoracic vertebral changes but stable cervical and hand findings, no white matter alterations

CaseEnzymeAssay: N/A

CaseUrineGAGs: At the age of 5 years, before ERT, were 18.2 μg/ml (nv: 5.27 μg/ml ± 3.01) with a CS/DS ratio of 25/75 (nv: 100/0); after 6, 9 and 10 year of ERT, plasma GAGs have remained within the normal range for age.

CaseERT: Yes

CaseBMT: N/A

Variant1: c.1205G>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 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