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FB2026_01
,
released March 12, 2026
This report describes mucopolysaccharidosis type IIIA (MPS3A), which is a subtype of mucopolysaccharidoses; MPS3A exhibits autosomal recessive inheritance. The human gene implicated in this disease is N-sulfoglucosamine sulfohydrolase (SGSH), which encodes one of several enzymes involved in the lysosomal degradation of heparan sulfate. There is a single orthologous gene in Drosophila, Sgsh, for which RNAi-targeting constructs have been generated.
The human SGSH has not been introduced into flies.
Pan-neuronal knockdown of Sgsh effected by RNAi results in significant accumulation of specific breakdown intermediates and a progressive locomotor (climbing) defect; this phenotype has been used as the basis of genetic screens for genes that interact with Sgsh.
Variants implicated in human disease have been introduced into flies, but have not been characterized. Variant(s) implicated in human disease (analogous mutation in fly gene): S301P in the fly Sgsh gene (corresponds to S298P in the human SGSH gene); S64W in the fly Sgsh gene (corresponds to S66W in the human SGSH gene).
[updated Oct. 2019 by FlyBase; FBrf0222196]
Lysosomal storage disease that involves the accumulation of glycosaminoglycans in the tissues and their excretion in the urine (DOID:12798)
The mucopolysaccharidoses are a group of inherited disorders caused by a lack of specific lysosomal enzymes involved in the degradation of glycosaminoglycans (GAGs), or mucopolysaccharides. The accumulation of partially degraded GAGs causes interference with cell, tissue, and organ function. [from MIM:607014; 2018.07.20]
[MUCOPOLYSACCHARIDOSIS, TYPE IIIA; MPS3A](https://omim.org/entry/252900)
[N-SULFOGLUCOSAMINE SULFOHYDROLASE; SGSH](https://omim.org/entry/605270)
The disorder is characterized by severe central nervous system degeneration, but only mild somatic disease. Onset of clinical features usually occurs between 2 and 6 years; severe neurologic degeneration occurs in most patients between 6 and 10 years of age, and death occurs typically during the second or third decade of life. [from MIM:252900; 2018.07.20]
Mucopolysaccharidosis type IIIA (MPS3A) is caused by homozygous or compound heterozygous mutation in the gene encoding N-sulfoglucosamine sulfohydrolase (SGSH). [from MIM:252900; 2018.07.20]
High concentrations of mucopolysaccharides in the cells of the central nervous system, including the brain, cause the neurological and developmental problems that accompany these disorders. MPS disorders are part of a larger group of disorders known as lysosomal storage disorders because the enzymes that break down mucopolysccharides are found within the lysosome. [NORD, Mucopolysaccharidosis Type III; 2018.07.20]
Genes implicated in mucopolysaccharidosis type III (MPS III, also known as Sanfilippo syndrome), encode enzymes that breakdown the mucopolysaccharide heparan sulphate. [Genetics Home Reference, Mucopolysaccharidosis type III; 2018.07.20]
The SGSH gene encodes sulfamidase, an enzyme located in lysosomes. Sulfamidase is involved in the step-wise breakdown of large sugars molecules called mucopolysaccharides or glycosaminoglycans (GAGs) during which individual sugars are removed one at a time from one end of the GAG chain. Sulfamidase removes a sulfate from a sugar called glucosamine when it is at the end of the GAG chain. [Genetics Home Reference, N-sulfoglucosamine sulfohydrolase; 2018.07.20]
MPS III includes 4 types, each due to the deficiency of a different enzyme: heparan N-sulfatase (type A); alpha-N-acetylglucosaminidase (type B); acetyl CoA:alpha-glucosaminide acetyltransferase (type C); and N-acetylglucosamine 6-sulfatase (type D). [from MIM:252900; 2018.07.20]
One to one: 1 human to 1 Drosophila.
High-scoring ortholog of human SGSH (1 Drosophila to 1 human). Dmel\CG14291 shares 55% identity and 67% similarity with the human gene.