Mutations in the GUSB gene reduce or completely eliminate the function of β-glucuronidase. The shortage (deficiency) of β-glucuronidase leads to
the accumulation of GAGs within cells, specifically inside the lysosomes. The accumulation of GAGs increases the size of the
lysosomes, which is why many tissues and organs are enlarged in this disorder.
How is Sly syndrome diagnosed?
Sly syndrome is diagnosed based on thorough clinical evaluation, identification of characteristic symptoms, detailed patient history. Specialized tests
that measure the level of beta-glucuronidase activity in skin fibroblasts or blood leukocytes is used for diagnosis. Diagnosis can be confirmed by
molecular genetic testing detecting mutations in the GUSB gene.
Prenatal diagnosis can be performed through chorionic villus biopsy or amniocentesis, if the mutations in the family are known.