Mucopolysaccharidoses

Mucopolysaccharidoses (MPS) are a family of inherited lysosomal storage disorders caused by deficient enzymes needed to degrade glycosaminoglycans (GAGs). GAGs accumulate in lysosomes across multiple tissues, producing progressive, multisystem disease that typically presents in childhood. Most forms are autosomal recessive; MPS II is X-linked.

Major MPS types include I (alpha-L-iduronidase deficiency), II (iduronate-2-sulfatase), III (Sanfilippo; various enzymes), IV (Morquio; A: N-acetylgalactosamine-6-sulfatase, B: beta-galactosidase), VI (arylsulfatase B), VII (beta-glucuronidase). MPS IX is extremely rare. Each type has a characteristic pattern of organ involvement, with some affecting the central nervous system more than others.

Common features are coarse facial appearance, skeletal deformities (dysostosis multiplex), short stature, joint stiffness, hepatosplenomegaly, and airway or cardiac complications. CNS involvement ranges from developmental delay to progressive dementia in certain types; vision and hearing impairment are frequent.

Diagnosis relies on clinical suspicion supported by urinary GAG testing, followed by enzyme activity assays and genetic testing to confirm the subtype.

Treatment is multidisciplinary. Enzyme replacement therapy is available for several forms (eg, MPS I, II, VI; Morquio A has approved therapy). Hematopoietic stem cell transplantation can improve outcomes in some patients, particularly when started early. Supportive care addresses respiratory, cardiac, orthopedic, and neurodevelopmental needs. Prognosis varies by type and severity and is notably better with early treatment.