The mucopolysaccharidoses are a group of inborn errors of metabolism caused by the deficiency of lysosomal hydrolases that degrade glycosaminoglycans (GAGs). These disorders are associated with a progressive accumulation of different types of GAGs within the cells of various organs and are characterized by somatic manifestations (facial dysmorphisms, hepatosplenomegaly, cardiac, respiratory, and skeletal involvement) and neurological, hematologic, and ocular symptoms. These manifestations are variably associated in each disorder. In most cases the disease phenotypes encompass a spectrum ranging from severe to attenuated clinical forms.
Because of the multisystem involvement in these patients, initial clinical assessment should include the evaluation of different organs and systems. Biochemical and genetic investigations are required to confirm the diagnosis. These include the analysis of urinary GAGs, the demonstration of a specific enzyme defect, and the identification of mutations in the relevant gene. For many of these disorders, prenatal diagnosis is possible either by direct assay of the deficient enzyme or by molecular analysis.
Management of all mucopolysaccharidoses requires supportive care and multidisciplinary treatment of a variety of systemic complications. Specific treatment is based on different approaches. Hematopoietic stem cell transplantation should be considered for MPS IH patients under the age of 2 years who have normal or near-normal developmental scores and for MPS VI patients.
Enzyme replacement therapy (ERT) with recombinant human enzymes is presently available for MPS IH/S and MPS IS, MPS II, and MPS VI and is under development for MPS IV. ERT results in improvement of somatic manifestations and of motor performance and in reduced GAG urinary excretion. However, other clinical features respond to a lesser extent to therapy; there is no evidence that any of the recombinant proteins cross the blood–brain barrier.
Other therapeutic approaches for the treatment of the mucopolysaccharidoses, such as substrate reduction therapy and gene therapy, are still experimental.
KeywordsHematopoietic Stem Cell Transplantation Enzyme Replacement Therapy Lysosomal Storage Disease Lysosomal Hydrolase Urinary GAGs
- Ellinwood NM, Ausseil J, Desmaris N, Bigou S, Liu S, Jens JK, Snella EM, Mohammed EE, Thomson CB, Raoul S, Joussemet B, Roux F, Chérel Y, Lajat Y, Piraud M, Benchaouir R, Hermening S, Petry H, Froissart R, Tardieu M, Ciron C, Moullier P, Parkes J, Kline KL, Maire I, Vanier MT, Heard JM, Colle MA (2011) Safe, efficient, and reproducible gene therapy of the brain in the dog models of Sanfilippo and Hurler syndromes. Mol Ther 19:251–259PubMedCentralPubMedCrossRefGoogle Scholar
- Malinowska M, Wilkinson FL, Langford-Smith KJ, Langford-Smith A, Brown JR, Crawford BE, Vanier MT, Grynkiewicz G, Wynn RF, Wraith JE, Wegrzyn G, Bigger BW (2010) Genistein improves neuropathology and corrects behaviour in a mouse model of neurodegenerative metabolic disease. PLoS One 5:e14192PubMedCentralPubMedCrossRefGoogle Scholar