Multiple sulfatase deficiency
Medical condition
From Wikipedia, the free encyclopedia
Multiple sulfatase deficiency (MSD), also known as Austin disease,[1] or mucosulfatidosis,[1] is a very rare autosomal recessive[2] lysosomal storage disease[3] caused by a deficiency in multiple sulfatase enzymes, or in formylglycine-generating enzyme, which activates sulfatases.[4]: 502 [5] It is similar to mucopolysaccharidosis.[6]
| Multiple sulfatase deficiency | |
|---|---|
| Other names | Juvenile sulfatidosis, Austin type |
| |
| Multiple sulfatase deficiency is autorecessive | |
| Specialty | Endocrinology  |
Signs and symptoms
Signs and symptoms of this disorder commonly appear between one and two years of age. Signs include mildly coarsened facial features, deafness, ichthyosis[7] and an enlarged liver and spleen (hepatosplenomegaly).[8] Abnormalities of the skeleton, such as a curving of the spine and breast bone may occur. Individuals afflicted with this disorder typically have dry skin.[9] Children affected by this disorder develop more slowly than normal and may display delayed speech and walking skills.[9]
The disease is fatal, with symptoms that include neurological damage and severe intellectual disability.[10] 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. As of 2018[update], 75–100 cases of MSD had been reported worldwide.[9]
Causes
Multiple sulfatase deficiency is caused by any mutation of the SUMF1 gene which renders its protein product, the formylglycine-generating enzyme (FGE), defective.[11][12] These mutations result in inactive forms of FGE.[13] This enzyme is required for posttranslational modification of a cysteine residue in the sulfatase enzyme active site into formylglycine,[14] which is required for its proper function.[15]
Genetics
MSD has an autosomal recessive inheritance pattern.[2] The inheritance probabilities per birth are as follows:
- If both parents are carriers:
- 25% (1 in 4) of children will have the disorder
- 50% (2 in 4) of children will be carriers (but unaffected)
- 25% (1 in 4) of 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
MSD may be diagnosed when deficiency of more than one sulfatase enzyme is identified in leukocytes or fibroblasts,[16] or by molecular genetic testing which shows pathogenic variation in both alleles of the SUMF1 gene.[9]
Treatment
As there is no cure for MSD, treatment is restricted to the management of symptoms.[16] There is much research on MSD that is currently underway. MSD Action Foundation has initiated more than 15 research projects on MSD in the last 6 years. Many of these have a translational focus. It is hoped that clinical trials for MSD will happen in the not-too-distant future- Alan Finglas. [Ref 17. Finglas 2020]