Multiple sulfatase deficiency | |
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Other names | Juvenile sulfatidosis, Austin type |
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Multiple sulfatase deficiency is autorecessive | |
Specialty |
Endocrinology
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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]
Symptoms of this disorder commonly appear between one and two years of age. Symptoms 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. The skin of individuals afflicted with this disorder, is typically dry. [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 mental retardation. [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]
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]
MSD has an autosomal recessive inheritance pattern. [2] The inheritance probabilities per birth are as follows:
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]
As there is no cure for MSD, treatment is restricted to management of symptoms. [16] 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]
[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
Multiple sulfatase deficiency | |
---|---|
Other names | Juvenile sulfatidosis, Austin type |
![]() | |
Multiple sulfatase deficiency is autorecessive | |
Specialty |
Endocrinology
![]() |
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]
Symptoms of this disorder commonly appear between one and two years of age. Symptoms 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. The skin of individuals afflicted with this disorder, is typically dry. [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 mental retardation. [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]
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]
MSD has an autosomal recessive inheritance pattern. [2] The inheritance probabilities per birth are as follows:
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]
As there is no cure for MSD, treatment is restricted to management of symptoms. [16] 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]
[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