MPSVII

MPS VII, or mucopolysaccharidosis type VII, is a rare lysosomal storage disorder caused by deficient activity of the enzyme beta-glucuronidase due to biallelic mutations in the GUSB gene. The enzyme deficiency leads to accumulation of glycosaminoglycans, particularly dermatan sulfate and heparan sulfate, in lysosomes throughout the body, producing multisystemic disease.

Clinical features are highly variable. Severe neonatal forms may present with nonimmune hydrops fetalis, hepatosplenomegaly, coarse facial features, skeletal dysplasia, and joint contractures. In milder cases, patients may have short stature, joint stiffness, dysostosis multiplex, hernias, recurrent respiratory infections, hearing loss, and organomegaly. Neurodevelopment is variable; severe disease can cause intellectual disability, while cognition may be less affected in some individuals. Eye involvement such as corneal clouding can occur, and cardiac valvular disease and spinal problems are additional complications.

Genetics: MPS VII is inherited in an autosomal recessive manner. The GUSB gene is located on chromosome 7q11.23. Carrier status is relevant for families, and consanguinity can increase risk.

Diagnosis: Suspicion is based on clinical findings. Definitive testing shows markedly reduced beta-glucuronidase activity in leukocytes or fibroblasts. Urinary glycosaminoglycans may be elevated but are not always diagnostic. GUSB gene sequencing confirms pathogenic variants.

Treatment and management: There is no cure. Enzyme replacement therapy with vestronidase alfa (Mepsevii) is approved to treat non-neurologic manifestations, but it does not cross the blood-brain barrier and does not address established neurological disease. Supportive care includes respiratory management, orthopedic interventions, physical therapy, and treatment of cardiac and hearing issues. Hematopoietic stem cell transplantation has been attempted in rare cases with limited success. Research into gene therapy and other approaches is ongoing.

Prognosis and epidemiology: MPS VII is exceedingly rare, with incidence well below 1 in a million. Prognosis depends on severity; severe forms shorten lifespan, while milder forms permit longer survival with chronic disability.