Multiple sulfatase deficiency (MSD), also known as Austin disease, or mucosulfatidosis, is a very rare

autosomal recessive In genetics, dominance is the phenomenon of one variant (allele) of a gene on a chromosome masking or overriding the Phenotype, effect of a different variant of the same gene on Homologous chromosome, the other copy of the chromosome. The firs ...

lysosomal storage disease caused by a deficiency in multiple sulfatase enzymes, or in formylglycine-generating enzyme, which activates sulfatases.Freedberg, et al. (2003). ''Fitzpatrick's Dermatology in General Medicine''. (6th ed.). McGraw-Hill. . It is similar to mucopolysaccharidosis.

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 Ichthyosis is a family of genetic disorder, genetic skin disorders characterized by Xeroderma, dry, Scleroderma, thickened, scaly skin. The more than 20 types of ichthyosis range in severity of symptoms, outward appearance, underlying genetic cau ...

and an enlarged liver and spleen ( hepatosplenomegaly). 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. 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

intellectual disability Intellectual disability (ID), also known as general learning disability (in the United Kingdom), and formerly mental retardation (in the United States), Rosa's Law, Pub. L. 111-256124 Stat. 2643(2010).Archive is a generalized neurodevelopmental ...

. These sulfatase enzymes are responsible for breaking down and recycling complex sulfate-containing sugars from

lipids Lipids are a broad group of organic compounds which include fats, waxes, sterols, fat-soluble vitamins (such as vitamins Vitamin A, A, Vitamin D, D, Vitamin E, E and Vitamin K, K), monoglycerides, diglycerides, phospholipids, and others. The fu ...

and mucopolysaccharides within the

lysosome A lysosome () is a membrane-bound organelle that is found in all mammalian cells, with the exception of red blood cells (erythrocytes). There are normally hundreds of lysosomes in the cytosol, where they function as the cell’s degradation cent ...

. The accumulation of lipids and mucopolysaccharides inside the lysosome results in symptoms associated with this disorder. , 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 In molecular biology, post-translational modification (PTM) is the covalent process of changing proteins following protein biosynthesis. PTMs may involve enzymes or occur spontaneously. Proteins are created by ribosomes, which translate mRNA ...

of a cysteine residue in the sulfatase enzyme active site into formylglycine, which is required for its proper function.

Genetics

MSD has an

inheritance pattern. 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 White blood cells (scientific name leukocytes), also called immune cells or immunocytes, are cells of the immune system that are involved in protecting the body against both infectious disease and foreign entities. White blood cells are genera ...

fibroblasts A fibroblast is a type of biological cell typically with a spindle shape that synthesizes the extracellular matrix and collagen, produces the structural framework ( stroma) for animal tissues, and plays a critical role in wound healing. Fibrobla ...

, or by molecular

genetic testing Genetic testing, also known as DNA testing, is used to identify changes in DNA sequence or chromosome structure. Genetic testing can also include measuring the results of genetic changes, such as RNA analysis as an output of gene expression, or ...

which shows pathogenic variation in both alleles of the SUMF1 gene.

Treatment

As there is no cure for MSD, treatment is restricted to the management of symptoms. 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. ef 17. Finglas 2020

References

7View 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

{{Posttranslational modification disorders Genodermatoses Autosomal recessive disorders Rare diseases Lipid storage disorders