Multiple Sulfatase Deficiency

Multiple sulfatase deficiency (also known as "Austin disease", and "mucosulfatidosis") is a very rare autosomal recessive^:561 lysosomal storage disease caused by a deficiency in multiple sulfatase enzymes, or in formylglycine-generating enzyme, which activates sulfatases.^:502 It is similar to mucopolysaccharidosis.

Signs and symptoms

Symptoms of this disorder commonly appear between one and two years of age. Symptoms include mildly coarsened facial features, deafness, ichthyosis and an enlarged liver and spleen (hepatosplenomegaly). Abnormalities of the skeleton, such as a curving of the spine and breast bone may occur. The skin of individuals afflicted with this disorder, is typically dry. Children affected by this disorder develop more slowly than normal and may display delayed speech and walking skills.

The disease is fatal, with symptoms that include neurological damage and severe mental retardation. These sulfatase enzymes are responsible for breaking down and recycling complex sulfate-containing sugars from lipids and mucopolysaccharides within the lysosome. The accumulation of lipids and mucopolysaccharides inside the lysosome results in symptoms associated with this disorder. Worldwide, forty cases of Multiple Sulfatase Deficiency have been reported to date.

Causes

Multiple sulfatase deficiency is thought to be caused by any mutation of the SUMF1 gene which would render its protein product, the formylglycine-generating enzyme (FGE), defective. These mutations result in inactive forms of FGE. This enzyme is required for posttranslational modification of a cysteine residue in the sulfatase enzyme active site into formylglycine, which is required for its proper function.

Genetics

MSD has an autosomal recessive inheritance pattern.^:561 The inheritance probabilities per birth are as follows:

• If both parents are carriers:
  • 25% (1 in 4) children will have the disorder
  • 50% (2 in 4) children will be carriers (but unaffected)
  • 25% (1 in 4) children will be free of MSD - unaffected child that is not a carrier
• If one parent is affected and one is free of MSD:
  • 0% (0) children will have the disorder - only one parent is affected, other parent always gives normal gene
  • 100% (4 in 4) children will be carriers (but unaffected)
• If one parent is a carrier and the other is free of MSD:
  • 50% (2 in 4) children will be carriers (but unaffected)
  • 50% (2 in 4) children will be free of MSD - unaffected child that is not a carrier

Diagnosis

Treatment

See also

• Linear porokeratosis
• List of cutaneous conditions