Diagnosis, classification and treatment of mucopolysaccharidosis type I

Abstract

Introduction: Mucopolysaccharidosis type I (MPS I) is a progressive lysosomal storage disease. Impaired degradation of glycosaminoglycans triggers complex pathophysiological cascades, leading to a heterogeneous multisystem disorder. Two treatment modalities are available: enzyme replacement therapy and hematopoietic stem cell transplantation. Despite these treatments, a significant residual disease burden is observed in most patients.

Areas covered: This review provides an overview of the currently known pathophysiological mechanisms underlying disease manifestations in MPS I. Additionally, the clinical presentation of the wide phenotypic spectrum is discussed, as well as methods for the phenotypical classification of patients and available treatment options, with a special focus on the treatment of residual disease.

Expert opinion: Residual disease is currently the most pressing issue in MPS I, often requiring multiple surgical interventions. Several strategies are being explored to decrease the residual disease burden including modifications to the current treatment regimens and new therapeutic approaches. Optimal management of disease manifestations requires international collaboration and a standardized follow-up to collect essential clinical data.

Keywords:

• classification
• diagnosis
• dysostosis multiplex
• mucopolysaccharodosis type I
• pathophysiology
• phenotype
• residual disease
• treatment

Declaration of interest

EJ Langereis has received consulting fee and travel grants from Genzyme/Sanofi. FA Wijburg has received consulting fee, travel grants and research grants from Shire Human Genetic Therapies, Genzyme/Sanofi and Actelion Pharmaceuticals. The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript. This includes employment, consultancies, honoraria, stock ownership or options, expert testimony, grants or patents received or pending, or royalties.

Notes

This box summarizes key points contained in the article.