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Published on: May 22, 2020
Enzyme-replacement therapy in a 5-month-old boy with attenuated presymptomatic MPS I: 5-year follow-up
Orazio Gabrielli1, Lorne A Clarke, Stefano Bruni
1Institute of Maternal-Infantile Sciences, Polytechnic University of Marche, Ancona, Italy. o.gabrielli@univpm.it
Abstract:
Mucopolysaccharidosis type I (MPS I) is a progressive and multisystemic disease, even in its attenuated Hurler-Scheie and Scheie forms. Clinical trials of enzyme-replacement therapy in MPS I have shown clinical benefit in patients with considerable preexisting disease, but no data exist on the effect of beginning enzyme replacement before the onset of significant clinical signs of disease. Here we present the 5-year follow-up of a boy with attenuated MPS I who had laronidase therapy initiated at the age of 5 months and compare his clinical course to that of his older sister, who began treatment at 5 years of age after she had developed typical signs of MPS I. After 5 years of treatment, the younger sibling has not developed any clinical manifestations of MPS I except for mild corneal clouding. In contrast, although many of the older sibling's clinical features have improved after 5 years of treatment, her dysostosis multiplex, cardiac valve involvement, and corneal clouding, although stabilized, have persisted. We suggest that early treatment of attenuated MPS I may significantly delay or prevent the onset of the major clinical signs, substantially modifying the natural history of the disease.
Insights
Early enzyme replacement therapy for Mucopolysaccharidosis type I (MPS I) in infants may prevent disease onset. This study suggests early intervention significantly alters the disease
Area of Science:
- Medical Genetics
- Biochemistry
- Pediatrics
Background:
- Mucopolysaccharidosis type I (MPS I) is a progressive genetic disorder affecting multiple body systems.
- Enzyme replacement therapy (ERT) with laronidase shows benefit in patients with established MPS I.
- Limited data exists on the efficacy of ERT initiated before significant clinical manifestation of attenuated MPS I.
Observation:
- A 5-year follow-up compares two siblings with attenuated MPS I.
- The younger sibling received laronidase at 5 months; the older sibling began treatment at 5 years.
- The younger sibling showed minimal symptoms, while the older sibling had persistent, though stabilized, disease features.
Findings:
- Early laronidase treatment in an infant with attenuated MPS I prevented most clinical manifestations.
- Late treatment in the older sibling improved some symptoms but did not resolve skeletal, cardiac, or ocular issues.
- Five years of early ERT resulted in significantly better clinical outcomes compared to later intervention.
Implications:
- Initiating ERT for attenuated MPS I in infancy may substantially alter the disease's natural progression.
- Early intervention could prevent or significantly delay the onset of major clinical signs of MPS I.
- This supports a strategy of proactive, early treatment for specific genetic disorders.
