• Source: Multiple sulfatase deficiency

Multiple sulfatase deficiency (MSD), also known as Austin disease, or mucosulfatidosis, is a very rare autosomal recessive 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. As of 2018, 75–100 cases of MSD had been reported worldwide.




Causes


Multiple sulfatase deficiency is caused by any mutation of the SUMF1 gene which renders 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.
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


MSD may be diagnosed when deficiency of more than one sulfatase enzyme is identified in leukocytes or fibroblasts, or by molecular genetic testing which shows pathogenic variation in both alleles of the SUMF1 gene.




Treatment


As there is no cure for MSD, treatment is restricted to management of symptoms.
There is much research on MSD that is currently underway. MSD Action Foundation have 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]




See also


Linear porokeratosis
List of cutaneous conditions




References



[17] View from inside: When multiple sulfatase deficiency changes everything about how you live and becomes your life
Alan Finglas,
https://doi.org/10.1002/jimd.12305




External links

Kata Kunci Pencarian:

• Multiple sulfatase deficiency
• Lysosomal storage disease
• Formylglycine-generating enzyme
• Hepatosplenomegaly
• MSD
• SUMF1
• List of diseases (M)
• Arylsulfatase A
• Lipid storage disorder
• List of skin conditions