Multiple sulphatase deficiency

Multiple sulphatase deficiency (MSD) is an inherited disorder that is caused by the accumulation of different compounds in cells throughout the body that cannot be broken down. This is due to a dysfunctional enzyme called formylglycine-generating enzyme. The most severe type of MSD has an onset of symptoms soon after birth, though the majority of children with MSD will begin to show symptoms in their first or second year of life. Tissue in the nervous system quickly begins to deteriorate, leading to movement problems, seizures, intellectual disability and slow development. Skeletal abnormalities may also be seen, as well as dry, scaly, itchy skin. Affected children usually have facial features that are referred to as "coarse" and some will have hearing loss. Major organs may also be affected, including the heart, liver and spleen. In rare cases, symptoms do not appear until mid-to late childhood. Typically survival is only for a few years after symptoms begin to show. There is no cure for MSD but medical surveillance and care may help to improve some symptoms and overall condition of life. MSD is caused by pathogenic variants in the SUMF1 gene.

MSD is inherited in an autosomal recessive manner. This type of inheritance requires the presence of two copies of a pathogenic variant for a person to have the genetic disease. Both parents must be carriers of a pathogenic variant in the gene in order to be at risk to have an affected child. The child must inherit a pathogenic variant from each carrier parent in order to be affected. There is a 1 in 4 chance that a baby will inherit two mutated copies of the gene and be affected when both parents are carriers.

There are generally no signs or symptoms associated with being a carrier for MSD. However, the risk to have a child affected with MSD is increased. Testing of reproductive partners is recommended for carriers of MSD.

MSD is estimated to affect 1 in 1,000,000 newborns worldwide.

The following websites may be informative: Genetic Home Reference: Multiple sulfatase deficiency (http://ghr.nlm.nih.gov/)

Gene Reviews: Leukodystrophy overview (http://www.ncbi.nlm.nih.gov/books/NBK1116/) OMIM: [272200: MULTIPLE SULFATASE DEFICIENCY] (http://www.ncbi.nlm.nih.gov/omim)

• Full gene sequencing