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. 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. , 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: 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 11 research projects on MSD in the last 4 years. Many of these have a translational focus. It is hoped that clinical trials for MSD will happen in the not too distant future. [Ref 17. Finglas 2020] References.  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