Multiple sulfatase deficiency

Multiple sulfatase deficiency (MSD), also known as Austin disease or mucosulfatidosis, is an ultra-rare inherited lysosomal storage disorder caused by mutations in the SUMF1 gene (also called FGE gene), which encodes the formylglycine-generating enzyme. This enzyme is essential for the post-translational activation of all sulfatase enzymes in the body. When it is deficient, all known sulfatases (at least 17 in humans) are simultaneously impaired, leading to the accumulation of sulfated substrates including sulfatides, mucopolysaccharides (glycosaminoglycans), and steroid sulfates in multiple tissues and organs. The clinical presentation of MSD combines features of several individual sulfatase deficiency disorders, including metachromatic leukodystrophy, multiple mucopolysaccharidoses, and X-linked ichthyosis. Key features include progressive neurological deterioration with developmental delay and regression, leukodystrophy, coarse facial features, skeletal abnormalities (dysostosis multiplex), hepatosplenomegaly, ichthyosis (dry, scaly skin), and hearing loss. Three clinical subtypes have been described based on age of onset and severity: a severe neonatal form, a late-infantile form (most common), and a rare juvenile form. The late-infantile form typically presents between ages one and four years with developmental regression and progressive neurological decline. There is currently no cure or disease-specific treatment for multiple sulfatase deficiency. Management is supportive and symptomatic, addressing seizures, respiratory complications, nutritional needs, and physical rehabilitation. Enzyme replacement therapy and gene therapy approaches are under investigation but remain experimental. Prognosis is generally poor, particularly in the neonatal and late-infantile forms, with most severely affected individuals surviving into childhood or early adolescence. Genetic counseling is recommended for affected families.

Data sourced from FDA regulatory filings and ClinicalTrials.gov. Updated periodically.

Common questions about Multiple sulfatase deficiency