Natural history and galsulfase treatment in mucopolysaccharidosis VI (MPS VI, Maroteaux-Lamy syndrome)--10-year follow-up of patients who previously participated in an MPS VI Survey Study.

Abstract

Mucopolysaccharidosis VI (MPS VI) is a clinically heterogeneous and progressive disorder with multiorgan manifestations caused by deficient N-acetylgalactosamine-4-sulfatase activity. A cross-sectional Survey Study in individuals (n = 121) affected with MPS VI was conducted between 2001 and 2002 to establish demographics, urinary glycosaminoglycan (GAG) levels, and clinical progression of disease. We conducted a Resurvey Study (ClinicalTrials.gov: NCT01387854) to obtain 10-year follow-up data, including medical histories and clinical assessments (n = 59), and survival status over 12 years (n = 117). Patients received a mean (SD) of 6.8 (2.2) years of galsulfase ERT between baseline (Survey Study) and follow-up. ERT patients increased in height by 20.4 cm in the 4-7-year-old baseline age group and by 16.8 cm in the 8-12-year-old baseline age group. ERT patients <13 years-old demonstrated improvement in forced vital capacity (FVC) by 68% and forced expiratory volume in 1 sec (FEV1) by 55%, and those ≥13 years-old increased FVC by 12.8% and maintained FEV1. Patients with >200 µg/mg baseline uGAG levels increased FVC by 48% in the <13-year-old baseline age group and by 15% in the ≥13-year-old baseline age group. ERT patients who completed the 6-min walk test demonstrated a mean (SD) increase of 65.7 (100.6) m. Cardiac outcomes did not significantly improve or worsen. Observed mortality rate among naïve patients was 50% (7/14) and 16.5% (17/103) in the ERT group (unadjusted hazard ratio, 0.24; 95% CI, 0.10-0.59). Long-term galsulfase ERT was associated with improvements in pulmonary function and endurance, stabilized cardiac function and increased survival.

• Authors: Roberto Giugliani, Christina Lampe, Nathalie Guffon, David Ketteridge, Elisa Leão-Teles, James E Wraith, Simon A Jones, Cheri Piscia-Nichols, Ping Lin, Adrian Quartel, Paul Harmatz
• Journal: American journal of medical genetics. Part A (Am J Med Genet A) Vol. 164A Issue 8 Pg. 1953-64 (Aug 2014) ISSN: 1552-4833 [Electronic] United States
• PMID: 24764221 (Publication Type: Journal Article, Multicenter Study, Research Support, N.I.H., Extramural, Research Support, Non-U.S. Gov't)
• Copyright: © 2014 Wiley Periodicals, Inc.

Chemical References

• Recombinant Proteins
• N-Acetylgalactosamine-4-Sulfatase
• galsulfase

Topics

• Adolescent
• Body Weights and Measures
• Child
• Child, Preschool
• Cross-Sectional Studies
• Enzyme Replacement Therapy
• Exercise Test
• Female
• Follow-Up Studies
• Heart Function Tests
• Humans
• Male
• Mucopolysaccharidosis VI (drug therapy, mortality, urine)
• N-Acetylgalactosamine-4-Sulfatase (therapeutic use, urine)
• Quality of Life
• Recombinant Proteins (therapeutic use, urine)
• Respiratory Function Tests
• Young Adult