Mucopolysaccharidosis type VII (also called Sly's disease) is the rarest form of lysosomal storage disease in the group of mucopolysaccharidoses.
The cause is an enzyme defect in the processing of glycosaminoglycans (GAGs). The patient lacks the enzyme beta-D-glucuronidase, which is required in the lysosomes for the degradation of GAGs dermatan sulfate, heparan sulfate and chondroitin 6-sulfate. The accumulation of these carbohydrates in the body tissue causes different degrees of damage.
These include in particular a characteristic physiognomy (pudgy face, large head, short neck, broad nose, thick lips, enlarged tongue) as well as progressive skeletal dysplasia, dwarfism and corneal and hearing disorders. In more severe cases, developmental delays may also occur
In 1973, the American pediatrician William S. Sly first described this autosomal recessive inherited form of MPS. Although fewer than 40 patients have been clearly identified since then, the number of unreported cases is assumed to be much higher. The spectrum ranges from severe forms (similar to M. Hurler), to forms with only a low skeletal involvement and normal mental development, so that those mildly affected patients are diagnosed only in adolescence or early adulthood.
The symptoms are extremely variable: there are prenatal forms with non-immunological hydrops fetalis characterized by early infant death, dysmorphism, hernias, hepatosplenomegaly, clubfoot, dysostosis, severe hypotonia and neurological disorders.
The prognosis is very bad, usually intrauterine fetal death occurs. It is believed that early deaths are often undiagnosed. Neonatal and infantile patients also have limited life expectancy, while patients with lighter forms survive longer.
On the other hand, there are also mild forms that only occur from adolescence or adulthood. In these forms, a kyphoscoliosis of the thorax is characteristic. The cause is a deficiency of beta-D-glucuronidase, which leads to the storage of various glycosaminoglycans in the lysosomes.