Mucopolysaccharidosis type 7

Mucopolysaccharidosis type VII (MPS VII), also known as Sly syndrome, is an extremely rare autosomal recessive lysosomal storage disorder caused by deficiency of the enzyme beta-glucuronidase (encoded by the GUSB gene on chromosome 7q11.21). This enzyme is essential for the degradation of glycosaminoglycans (GAGs), specifically dermatan sulfate, heparan sulfate, and chondroitin sulfate. When beta-glucuronidase is deficient, these GAGs accumulate progressively in lysosomes throughout the body, leading to widespread cellular and organ damage. MPS VII presents with a remarkably wide clinical spectrum, ranging from severe hydrops fetalis (fluid accumulation in the fetus, which can be lethal before or shortly after birth) to milder forms with later onset. Common features include skeletal abnormalities (dysostosis multiplex), short stature, hepatosplenomegaly (enlarged liver and spleen), coarse facial features, corneal clouding, hernias, recurrent respiratory infections, and cardiac valve disease. Many patients experience intellectual disability of varying severity, though some individuals with milder forms may have normal or near-normal cognitive function. Joint stiffness and restricted mobility are also frequently observed. Treatment for MPS VII includes enzyme replacement therapy (ERT) with vestronidase alfa (Mepsevii), which was approved by the FDA in 2017 and by the EMA in 2018, making it the first ERT specifically approved for this condition. Vestronidase alfa works by providing a recombinant form of beta-glucuronidase to help break down accumulated GAGs. Hematopoietic stem cell transplantation (HSCT) has also been used in some patients, particularly early in life, with the goal of providing a permanent source of the deficient enzyme. Supportive and symptomatic management—including orthopedic interventions, cardiac monitoring, respiratory support, and developmental therapies—remains an important component of care. Due to the rarity and variability of the disease, management should be coordinated by a multidisciplinary team experienced in lysosomal storage disorders.

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