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 effect of a different variant of the same gene on the other copy of the chromosome. The first variant is termed dominant and t ...

James, William; Berger, Timothy; Elston, Dirk (2005). ''Andrews' Diseases of the Skin: Clinical Dermatology''. (10th ed.). Saunders. .

lysosomal storage disease Lysosomal storage diseases (LSDs; ) are a group of over 70 rare inherited metabolic disorders that result from defects in lysosomal function. Lysosomes are sacs of enzymes within cells that digest large molecules and pass the fragments on to other ...

caused by a deficiency in multiple

sulfatase Sulfatases are enzymes of the esterase class that catalyze the hydrolysis of sulfate esters. These may be found on a range of substrates, including steroids, carbohydrates and proteins. Sulfate esters may be formed from various alcohols and amin ...

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 Mucopolysaccharidoses are a group of metabolic disorders caused by the absence or malfunctioning of lysosome, lysosomal enzymes needed to break down molecules called glycosaminoglycans (GAGs). These long chains of sugar carbohydrates occur within ...

Signs and symptoms

Symptoms of this disorder commonly appear between one and two years of age. Symptoms include mildly coarsened facial features, deafness,

ichthyosis Ichthyosis is a family of genetic skin disorders characterized by dry, thickened, scaly skin. The more than 20 types of ichthyosis range in severity of symptoms, outward appearance, underlying genetic cause and mode of inheritance (e.g., dominan ...

and an enlarged liver and spleen (

hepatosplenomegaly Hepatosplenomegaly (commonly abbreviated HSM) is the simultaneous enlargement of both the liver (hepatomegaly) and the spleen (splenomegaly). Hepatosplenomegaly can occur as the result of acute viral hepatitis, infectious mononucleosis, and hist ...

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

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

lipids Lipids are a broad group of naturally-occurring molecules which includes fats, waxes, sterols, fat-soluble vitamins (such as vitamins A, D, E and K), monoglycerides, diglycerides, phospholipids, and others. The functions of lipids include ...

and mucopolysaccharides within the

lysosome A lysosome () is a membrane-bound organelle found in many animal cells. They are spherical vesicles that contain hydrolytic enzymes that can break down many kinds of biomolecules. A lysosome has a specific composition, of both its membrane prot ...

. 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 Post-translational modification (PTM) is the covalent and generally enzymatic modification of proteins following protein biosynthesis. This process occurs in the endoplasmic reticulum and the golgi apparatus. Proteins are synthesized by ribosome ...

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) 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 White blood cells, also called leukocytes or leucocytes, are the cells of the immune system that are involved in protecting the body against both infectious disease and foreign invaders. All white blood cells are produced and derived from mult ...

fibroblasts A fibroblast is a type of biological cell that synthesizes the extracellular matrix and collagen, produces the structural framework ( stroma) for animal tissues, and plays a critical role in wound healing. Fibroblasts are the most common cells o ...

, 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 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. 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