Early treatment with laronidase improves clinical outcomes in patients with attenuated MPS I: a retrospective case series analysis of nine sibships. Issue 1 (December 2015)

• Record Type: Journal Article
• Authors: Al-Sannaa, Nouriya; Bay, Luisa; Barbouth, Deborah; Benhayoun, Youssef; Goizet, Cyril; Guelbert, Norberto; Jones, Simon; Kyosen, Sandra; Martins, Ana; Phornphutkul, Chanika; Reig, Celia; Pleat, Rebecca; Fallet, Shari; Ivanovska Holder, Iva
• Is Part Of: Orphanet journal of rare diseases. Volume 9:Issue 1(2014)
• Page Start: 1
• Page End: 9
• Publication Date: 2015-12
• Subjects: Enzyme replacement therapy -- Early diagnosis -- Early treatment; Rare diseases -- Periodicals; Genetic disorders -- Periodicals; Orphan drugs -- Periodicals; 616
• DOI: 10.1186/s13023-015-0344-4
• Languages: English
• ISSNs: 1750-1172

Abstract

Abstract Background Enzyme replacement therapy (ERT) with laronidase, (recombinant human α-L-iduronidase; Aldurazyme) is the primary treatment option for patients with attenuated mucopolysaccharidosis type I (MPS I). This study examined the effect of early ERT on clinical manifestations. Methods This multinational, retrospective case series abstracted data from records of 20 patients with Hurler-Scheie syndrome within nine sibships that included older siblings treated with laronidase after the development of significant clinical symptoms, and younger siblings treated before significant symptomatology. Median age at diagnosis was 5.6 and 0.5 years for older and younger siblings, respectively. Median age at ERT initiation was 7.9 and 1.9 years for older and younger siblings, respectively. Results Improvement or stabilization of somatic signs and symptoms was more notable in younger siblings. Organomegaly present at onset of ERT improved in the majority of both older and younger siblings. Analysis of physician-rated symptom severity demonstrated that cardiac, musculoskeletal, and cognitive symptoms, when absent or mild in younger siblings at ERT initiation, generally did not develop or progress. The majority of older siblings had height/length Z-scores greater than two standard deviations below the mean (less than -2) at both time points. In general, Z-scores for younger siblings were closer to the sex- and age-matched means at follow-up. Conclusions These findings suggest early initiation of laronidase, prior to the onset of symptoms in patients with attenuated MPS I, can slow or prevent the development of severe clinical manifestations.