Long-term outcomes of systemic therapies for Hurler syndrome: an international multicenter comparison

Abstract

Purpose Early treatment is critical for mucopolysaccharidosis type I (MPS I), justifying its incorporation into newborn screening. Enzyme replacement therapy (ERT) treats MPS I, yet presumptions that ERT cannot penetrate the blood-brain barrier (BBB) support recommendations that hematopoietic cell transplantation (HCT) treat the severe, neurodegenerative form (Hurler syndrome). Ethics preclude randomized comparison of ERT to HCT, but insight into this comparison is presented with an international cohort of patients with Hurler syndrome who received long-term ERT from a young age. Methods Long-term survival and neurologic outcomes were compared among three groups of patients with Hurler syndrome: 18 treated with ERT monotherapy (ERT group), 54 who underwent HCT (HCT group), and 23 who received no therapy (Untreated). All were followed starting before age 5 years. A sensitivity analysis restricted age below 3 years. Results Survival was worse when comparing ERT versus HCT, and Untreated versus ERT. The cumulative incidences of hydrocephalus and cervical spinal cord compression were greater in ERT versus HCT. Findings persisted in the sensitivity analysis. Conclusion As newborn screening widens treatment opportunity for Hurler syndrome, this examination of early treatment quantifies some ERT benefit, supports presumptions about BBB impenetrability, and aligns with current guidelines to treat with HCT.

Intravenous Enzyme Replacement Therapy in Mucopolysaccharidoses: Clinical Effectiveness and Limitations

“…Furthermore, similar issues are observed for all types of MPSs: there are tissues where the efficacy of the recombinant enzyme is limited by scarce penetration, like eyes, cartilage and bones, and tissues that cannot be repaired having an already-established damage at time of start of ERT [24]. A recent comparison between MPS I-Hurler patients treated with HSCT and others treated with only ERT showed impressive differences in hydrocephalus and cord-compression incidence in the two groups: 0% and 16%, respectively, for the HSCT-treated and 40% and 67%, respectively, for the ERT-only-treated patients [25]. The use of ERT in patients who develop severe cognitive decline might be questioned.…”

Diagnostic precision and identification of rare diseases is dependent on distance of residence relative to tertiary medical facilities

“…In Glucose transporter-1 de ciency syndrome ketogenic diet reduces the frequency of seizures and severity of motoric impairment (24). Early treatment in patients with Hurler Syndrome (mucopolysaccharidosis type 1) prevents cognitive and physical disability (25). So an early and precise diagnosis is crucial.…”

Structure-Function Relationship of Heart Valves in Health and Disease

“…A number of congenital enzyme deficiencies have been linked to GAG metabolic disorders (mucopolysaccharidoses) [13]. Among mucopolysaccharidoses, the Hurler [56][57][58][59] and Hunter [60][61][62] syndromes are the most widely studied. Mucopolysaccharidoses are associated with mutations in the gene encoding lysosomal hydrolases, including endoglycosidases and exoglycosidases, which are enzymes involved in GAG degradation [56,57,62].…”