Clinical Information

Multiple sulfatase deficiency (MSD) is a rare autosomal recessive lysosomal disorder caused by mutations in the sulfatase-modifying factor 1 (SUMF1) gene. SUMF1 encodes for a formylglycine-generating enzyme that performs a critical posttranslational modification necessary for activation of all human sulfatases, including arylsulfatase A and B. The clinical features of MSD encompass symptoms of every single sulfatase deficiency, including metachromatic leukodystrophy (MLD), the mucopolysaccharidoses, X-linked ichthyosis, and chondrodysplasia punctata type I. Age of onset and clinical severity are variable and correspond with the level of residual enzyme activity. A severe neonatal form of MSD closely overlaps the clinical presentation of the mucopolysaccharidoses, but it is often fatal within 1 year. Late-infantile MSD (onset 0-2 years) accounts for most cases and is characterized by a clinical presentation similar to MLD.

A diagnostic workup for MSD demonstrates reduced enzyme activity of several sulfatase enzymes including those on this panel (iduronate-2-sulfatase, heparan sulfate sulfatase, galactosamine-6-sulfate sulfatase, and arylsulfatase B). Individuals with MSD typically have an increased urinary excretion of sulfatides as well as increased urinary glycosaminoglycans, therefore a combined analysis of urine ceramide trihexoside, mucopolysaccharides, oligosaccharides, and sulfatides (LSDS/ Lysosomal Storage Disorders Screen, Random, Urine) may support a diagnosis. Molecular genetic analysis of the SUMF1 gene (CGPH / Custom Gene Panel, Hereditary, Next-Generation Sequencing, Varies; specify Gene List ID: IEMCP-PCUBX1) allows for detection of disease-causing variants in affected patients and subsequent carrier detection in relatives.