Chapter 9 - Lysosomal storage disorders: Mucopolysaccharidoses

Abstract

Mucopolysaccharidoses (MPS) are lysosomal storage diseases characterized by deficient degradation of mucopolysaccharides or glycosaminoglycans (GAGs). Abnormal storage of dermatan sulfate, heparan sulfate, keratan sulfate, or hyaluronan occurs in all seven types of MPS due to a deficiency in one of the enzymes in the catabolic pathways of GAGs. MPS disorders are usually multisystemic, with progressive involvement of brain, visceral organs, and bones. However, patients with MPS type IV and VI generally do not have cognitive impairment or central nervous system (CNS) involvement. The characteristic skeletal abnormalities are unique features of MPS IV or Morquio syndrome that are not seen in other types of MPS. Most individuals with MPS appear normal at birth and clinical features develop over time. Each type of MPS has classic or severe presentations as well as attenuated disease forms. Urinary GAG analysis is useful for differential diagnosis and detects total elevations as well as elevated species of GAGs. More recently, liquid chromatography tandem mass spectrometry analysis of GAG-specific disaccharides generated by either enzyme digestion or methanolysis provides a more specific and sensitive solution for screening and monitoring patients with MPS. Enzyme replacement therapy (ERT) has been the mainstay for treating several of the MPSs. Food and Drug Administration approved ERT are available for MPS I, II, IV, and VI. Other therapeutic modalities to target-specific tissues, such as CNS, are being investigated.