Clinical outcomes of exclusive enzyme therapy (laronidase) in a cohort of patients with mucopolysaccharidosis type I

Abstract Background Mucopolysaccharidosis type I (MPS I), is an autosomal recessive disorder caused by a deficiency in the enzyme α-L-iduronidase (IDUA), leading to the accumulation of glycosaminoglycans (GAGs) in tissues. Early diagnosis and treatment [i.e., bone marrow transplantation and/or enzyme replacement therapy (ERT) with laronidase] are essential to prevent irreversible damage. The long-term effectiveness of exclusive ERT has been primarily described in attenuated phenotypes, while only a few cases have been reported in severe phenotypes. Methods This study is a retrospective analysis summarising the collective experience of disease progression in 48 patients with severe and attenuated MPS I who were treated exclusively with laronidase over a median of 10 years at the Lyon Reference Centre for Hereditary Metabolic Diseases in France. Patients were categorised by genotype and further stratified by age at treatment initiation. The study assessed the evolution of urinary excretion of GAGs, pulmonary function, cardiac involvement and evolution, height, cognitive impairment, functional status, orthopaedic and ear-nose-throat (ENT) procedures, sleep apnoea, and carpal tunnel syndrome. Descriptive statistical analysis methods were used. Results ERT reduced the GAGus levels by 88% in severe MPS I and by 71% in attenuated MPS I, of which 47% and 65% patients, respectively achieved normal age-related GAG levels at the last follow-up. ERT provided stable or consistent improvement in forced vital capacity, slowed progression of adverse cardiac course and improved auditory transmission in majority of the severe and attenuated patients. At the last follow-up, 84% attenuated patients had normal cognitive development. In alive Hurler patients, cognitive development was very heterogenous; however, 73% patients had a developmental quotient (DQ) ≥ 70. Laronidase was effective in improving statural growth of attenuated patients treated before 9 years of age. Conclusion Early ERT and regular multidisciplinary management are effective in slowing disease progression in severe and attenuated patients with MPS I and helping to maintain autonomy in patients with attenuated MPS I, ensuring a better quality of life.