pediatrics
Overview of Lysosomal Storage Disorders
Mucopolysaccharidoses (MPS)
MPS are inherited deficiencies of enzymes involved in glycosaminoglycan breakdown. Glycosaminoglycans (previously termed mucopolysaccharides) are polysaccharides abundant on cell surfaces and in extracellular matrix and structures. Enzyme deficiencies that prevent glycosaminoglycan breakdown cause accumulation of glycosaminoglycan fragments in lysosomes and cause extensive bone, soft tissue, and central nervous system changes. Inheritance is usually Autosomal Recessive (except for MPS type II). Age at presentation, clinical manifestations, and severity vary by type (see table Mucopolysaccharidosis (MPS) ). Common manifestations include coarse facial features, neurodevelopmental delays and regression, joint contractures, organomegaly, stiff hair, progressive respiratory insufficiency (caused by airway obstruction and sleep apnea), cardiac valvular disease, skeletal changes, and cervical vertebral subluxation. Diagnosis of mucopolysaccharidoses is suggested by history, physical examination, bone abnormalities (eg, dysostosis multiplex) found during skeletal survey, and elevated total and fractionated urinary glycosaminoglycans. Diagnosis is confirmed by DNA analysis and/or enzyme analysis of cultured fibroblasts (prenatal) or peripheral white blood cells (postnatal). (Also see Initial testing .) Additional testing is required to monitor organ-specific changes (eg, echocardiography for valvular disease, audiometry for hearing changes). Treatment of mucopolysaccharidosis type I is enzyme replacement withlaronidase, which effectively halts progression and reverses all non-central nervous system complications of the disease. Hematopoietic stem cell (HSC) transplantation has also been used. The combination of enzyme replacement and HSC transplantation is under study. For patients with MPS type IV-A (Morquio A syndrome), enzyme replacement withelosulfase alfamay improve functional status, including mobility. 