Early treatment with laronidase improves clinical outcomes in patients with attenuated MPS I: a retrospective case series analysis of nine sibships.
Orphanet J Rare Dis. 2015-10-07; 10(1):
DOI: 10.1186/s13023-015-0344-4
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1. Orphanet J Rare Dis. 2015 Oct 7;10:131. doi: 10.1186/s13023-015-0344-4.
Early treatment with laronidase improves clinical outcomes in patients with
attenuated MPS I: a retrospective case series analysis of nine sibships.
Al-Sannaa NA(1), Bay L(2), Barbouth DS(3), Benhayoun Y(4), Goizet C(5), Guelbert
N(6), Jones SA(7), Kyosen SO(8), Martins AM(8), Phornphutkul C(9), Reig C(10),
Pleat R(11), Fallet S(11)(12), Ivanovska Holder I(13).
Author information:
(1)Johns Hopkins Aramco Healthcare, Dhahran, Saudi Arabia.
(2)Department of Inherited Errors of Metabolism, Hospital Juan P. Garrahan,
Buenos Aires, Argentina.
(3)Dr. John T. Macdonald Foundation, Department of Human Genetics, University of
Miami Miller School of Medicine, Miami, FL, USA.
(4)Pediatric Services, Robert Boulin Hospital, Libourne, France.
(5)CHU Bordeaux, Pellegrin Hospital, Department and Univ. Bordeaux, laboratoire
MRGM (EA4576), Bordeaux, France.
(6)Metabolic Section, Children’s Hospital of Córdoba, Córdoba, Argentina.
(7)Manchester Centre for Genomic Medicine, St. Mary’s Hospital, CMFT, University
of Manchester, Manchester, UK.
(8)Reference Center for Inborn Errors of Metabolism, Federal University of São
Paulo, São Paulo, Brazil.
(9)Division of Human Genetics, Department of Pediatrics, Hasbro Children’s
Hospital, Brown University, Providence, RI, USA.
(10)Pediatric Division, General Hospital of Segovia, Segovia, Spain.
(11)Genzyme, a Sanofi company, 500 Kendall Street, Cambridge, MA, 02142, USA.
(12)Pfizer Inc, New York City, NY, USA.
(13)Genzyme, a Sanofi company, 500 Kendall Street, Cambridge, MA, 02142, USA.
.
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.
DOI: 10.1186/s13023-015-0344-4
PMCID: PMC4597395
PMID: 26446585 [Indexed for MEDLINE]