Early treatment with laronidase improves clinical outcomes in patients with attenuated MPS I: a retrospective case series analysis of nine sibships.

Autor: Al-Sannaa NA; Johns Hopkins Aramco Healthcare, Dhahran, Saudi Arabia., Bay L; Department of Inherited Errors of Metabolism, Hospital Juan P. Garrahan, Buenos Aires, Argentina., Barbouth DS; Dr. John T. Macdonald Foundation, Department of Human Genetics, University of Miami Miller School of Medicine, Miami, FL, USA., Benhayoun Y; Pediatric Services, Robert Boulin Hospital, Libourne, France., Goizet C; CHU Bordeaux, Pellegrin Hospital, Department and Univ. Bordeaux, laboratoire MRGM (EA4576), Bordeaux, France., Guelbert N; Metabolic Section, Children's Hospital of Córdoba, Córdoba, Argentina., Jones SA; Manchester Centre for Genomic Medicine, St. Mary's Hospital, CMFT, University of Manchester, Manchester, UK., Kyosen SO; Reference Center for Inborn Errors of Metabolism, Federal University of São Paulo, São Paulo, Brazil., Martins AM; Reference Center for Inborn Errors of Metabolism, Federal University of São Paulo, São Paulo, Brazil., Phornphutkul C; Division of Human Genetics, Department of Pediatrics, Hasbro Children's Hospital, Brown University, Providence, RI, USA., Reig C; Pediatric Division, General Hospital of Segovia, Segovia, Spain., Pleat R; Genzyme, a Sanofi company, 500 Kendall Street, Cambridge, MA, 02142, USA., Fallet S; Genzyme, a Sanofi company, 500 Kendall Street, Cambridge, MA, 02142, USA.; Pfizer Inc, New York City, NY, USA., Ivanovska Holder I; Genzyme, a Sanofi company, 500 Kendall Street, Cambridge, MA, 02142, USA. Iva.IvanovskaHolder@genzyme.com.
Jazyk: angličtina
Zdroj: Orphanet journal of rare diseases [Orphanet J Rare Dis] 2015 Oct 07; Vol. 10, pp. 131. Date of Electronic Publication: 2015 Oct 07.
DOI: 10.1186/s13023-015-0344-4
Abstrakt: 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.
Databáze: MEDLINE
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