Mucopolysaccharidosis type VII (MPS VII), or Sly syndrome, is a rare autosomal recessive lysosomal storage disorder caused by deficiency of the enzyme β-glucuronidase. This enzymatic defect leads to the accumulation of glycosaminoglycans - particularly heparan sulfate, dermatan sulfate, and chondroitin 4- and 6-sulfate - in various tissues, resulting in progressive multisystem involvement. Clinical presentation is highly variable, ranging from severe forms with non-immune hydrops fetalis or early, severe multisystem manifestations, to milder, attenuated phenotypes with later onset, normal or near-normal intelligence, and survival into adulthood.
Postnatal growth deficiency and short stature are common, alongside distinctive craniofacial features such as macrocephaly, coarse facies, thick eyebrows, coarse hair, macroglossia, gingival hypertrophy, and small/widely spaced teeth. Sensorineural hearing loss and variable corneal clouding may occur. Other common ocular features include visual impairment, and photosensitivity.
Cardiopulmonary involvement includes valvular heart disease, cardiomyopathy, decreased pulmonary function, obstructive airway disease, sleep apnoea, chronic bronchitis, and recurrent respiratory infections.
Abdominal findings frequently include hepatosplenomegaly and umbilical or inguinal hernias.
The skeletal phenotype is consistent with dysostosis multiplex, including scoliosis, kyphosis, platyspondyly, gibbus deformity, odontoid hypoplasia, and pelvic dysplasia.
Thoracic abnormalities may include short trunk, pectus carinatum or excavatum, and rib cage deformities. Joint contractures, genu valgum, and foot anomalies such as talipes equinovarus and metatarsus adductus are also observed. Patients also may present loss of range of motion, with restricted mobility. Hand abnormalities include clawed hands and curved fingers.
Neurologically, patients may present with developmental delay, intellectual disability, poor speech, hydrocephalus, and progressive neurodegeneration.
Progression of disease is variable. In general, patients with milder phenotype usually deteriorate more slowly than patients with more severe phenotype.
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