This report describes mucopolysaccharidosis type I (MPS I): MPS I exhibits autosomal recessive inheritance. OMIM categorizes this disease as 3 sub-types, based on severity: Hurler syndrome (MPS IH; MIM:607014), Scheie syndrome (MPS IS; MIM:607016), and Hurler-Scheie syndrome (MPS IH/S; MIM:607015). The human gene implicated in MPS I is IDUA, an enzyme required for lysosomal degradation of two glycosaminoglycans, dermatan sulfate and heparan sulfate. There is a single orthologous gene in Drosophila, Dmel\Idua, for which a small number of genetic reagents have been generated including RNAi-targeting constructs and a targeted CRISPR knockout construct.
The human IDUA gene has not been introduced into Drosophila.
Ubiquitous reduction of Dmel\Idua expression, effected by RNAi, results to lethality during the pupal stage; RNAi targeted to muscle also results in complete lethality at the pupal stage. Knockdown specifically in neurons or glia allows survival to adulthood; progressive locomotor defects are observed. Assessed in third instar larvae, dysfunctions of lysosomes and the autophagic pathway, with metabolic changes in glycolysis and lipogenesis, are observed. Starvation significantly ameliorates these phenotypes.
[updated Jan. 2022 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 I (MPS I) is a progressive multisystem disorder with features ranging over a continuum of severity. While affected individuals have traditionally been classified as having one of three MPS I syndromes (Hurler syndrome, Hurler-Scheie syndrome, or Scheie syndrome), no easily measurable biochemical differences have been identified and the clinical findings overlap. (Gene Reviews, Mucopolysaccharidosis Type I; 2022.01.16]
The clinical features of Hurler syndrome, the most severe sub-type, include coarse facies, corneal clouding, mental retardation, hernias, dysostosis multiplex, and hepatosplenomegaly. Children with Hurler syndrome appear normal at birth and develop the characteristic appearance over the first years of life (Wraith et al., 1987; pubmed:3124802). [from MIM:607014; 2022.01.16]
Deficiency of alpha-L-iduronidase can result in a wide range of phenotypic involvement with 3 major recognized clinical entities: Hurler (MPS IH; MIM:607014), Scheie (MPS IS; MIM:607016), and Hurler-Scheie (MPS IH/S; MIM:607015) syndromes. Hurler and Scheie syndromes represent phenotypes at the severe and mild ends of the MPS I clinical spectrum, respectively, and the Hurler-Scheie syndrome is intermediate in phenotypic expression (McKusick, 1972). [from MIM:607015; 2022.01.16]
Hurler syndrome, Scheie syndrome, and Hurler-Scheie syndrome are caused by homozygous or compound heterozygous mutation in the gene encoding alpha-L-iduronidase (IDUA). [from MIM:607014, MIM:607015, MIM:607016; 2022.01.16]
The IDUA gene encodes Alpha-L-Iduronidase, an enzyme that hydrolyzes the terminal alpha-L-iduronic acid residues of two glycosaminoglycans, dermatan sulfate and heparan sulfate. This hydrolysis is required for the lysosomal degradation of these glycosaminoglycans. [Gene Cards, IDUA; 2022.01.16]
One to one: 1 human gene to 1 Drosophila gene.
High-scoring ortholog of human IDUA (1 Drosophila to 1 human).
