This report describes mucopolysaccharidosis type IIIC, a subtype of progeria that exhibits autosomal recessive inheritance. The human gene implicated is HGSNAT, which encodes heparan-alpha-glucosaminide N-acetyltransferase, one of several enzymes involved in the lysosomal degradation of heparin sulfate. There is one high-scoring fly ortholog, Dmel\Hgsnat, for which multiple genetic reagents, including classical alleles, RNAi-targeting constructs, and alleles caused by insertional mutagenesis, have been generated.
Human HGSNAT has not been introduced into flies.
Flies mutant for Hgsnat exhibit a progressive accumulation of heparin sulfuate; this is also observed in flies undergoing ubiquitous RNAi-mediated knockdown of Dmel\Hgsnat. Ubiquituous RNAi-mediated knockdown also results in a significantly shortened lifespan. Pan-neuronal RNAi-mediated knockdown of Dmel\Hgsnat results in enlargement of the endolysosomal compartment in the brain, presynaptic abnormalities, and locomotor defects. RNAi-mediated knockdown of Dmel\Hgsnat in cortex and wrapping glia resulted in climbing defects in adult flies, while knockdown in sub-perineurial glia and astrocytes impaired activity in an activity monitor assay.
[updated Apr. 2024 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 IIIC; MPS3C](https://omim.org/entry/252930)
[HEPARAN-ALPHA-GLUCOSAMINIDE N-ACETYLTRANSFERASE; HGSNAT](https://omim.org/entry/610453)
Mucopolysaccharidosis type III (MPS III) is a multisystem lysosomal storage disease characterized by progressive central nervous system degeneration manifest as severe intellectual disability (ID), developmental regression, and other neurologic manifestations including autism spectrum disorder (ASD), behavioral problems, and sleep disturbances. Disease onset is typically before age ten years. Disease course may be rapidly or slowly progressive; some individuals with an extremely attenuated disease course present in mid-to-late adulthood with early-onset dementia with or without a history of ID. Systemic manifestations can include musculoskeletal problems (joint stiffness, contractures, scoliosis, and hip dysplasia), hearing loss, respiratory tract and sinopulmonary infections, and cardiac disease (valvular thickening, defects in the cardiac conduction system). Neurologic decline is seen in all affected individuals; however, clinical severity varies within and among the four MPS III subtypes (defined by the enzyme involved) and even among members of the same family. Death usually occurs in the second or third decade of life secondary to neurologic regression or respiratory tract infections. [from GeneReviews, Mucopolysaccharidosis Type III; 2024.04.03]
Sanfilippo syndrome comprises several forms of lysosomal storage diseases due to impaired degradation of heparan sulfate. The deficient enzyme in Sanfilippo syndrome C, or MPS IIIC, is an acetyltransferase that catalyzes the conversion of alpha-glucosaminide residues to N-acetylglucosaminide in the presence of acetyl-CoA. [from MIM:252930; 2024.04.03]
Mucopolysaccharidosis type IIIC (MPS3C), also known as Sanfilippo syndrome C, is caused by homozygous or compound heterozygous mutation in the HGSNAT gene, encoding heparan acetyl- CoA:alpha-glucosaminide N-acetyltransferase, on chromosome 8p11. [from MIM:252930; 2024.04.03]
One to one (1 human to 1 Drosophila); HGSNAT has one high-scoring Drosophila ortholog, Hgsnat.
High-scoring ortholog of human HGSNAT (1 Drosophila to 1 human).
