Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: EC:5.4.2.8 (phosphomannomutase)
 238 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Carbohydrate-deficient glycoprotein syndrome type 1 (CDG1 or Jaeken syndrome) is the prototype of a class of genetic multisystem disorders characterized by defective glycosylation of glycoconjugates. It is mostly a severe disorder which presents neonatally. There is a severe encephalopathy with axial hypotonia, abnormal eye movements and pronounced psychomotor retardation, as well as a peripheral neuropathy, cerebellar hypoplasia and retinitis pigmentosa. The patients show a peculiar distribution of subcutaneous fat, nipple retraction and hypogonadism. There is a 20% lethality in the first years of life due to severe infections, liver insufficiency or cardiomyopathy. CDG1 shows an autosomal recessive mode of inheritance and has been mapped to chromosome 16p. Most patients show a deficiency of phosphomannomutase (PMM)8, an enzyme necessary for the synthesis of GDP-mannose. We have cloned the PMM1 gene, which is on chromosome 22q13 (ref.9). We now report the identification of a second human PMM gene, PMM2, which is located on 16p13 and which encodes a protein with 66% identity to PMM1. We found eleven different missense mutations in PMM2 in 16 CDG1 patients from different geographical origins and with a documented phosphomannomutase deficiency. Our results give conclusive support to the biochemical finding that the phosphomannomutase deficiency is the basis for CDG1.
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PMID:Mutations in PMM2, a phosphomannomutase gene on chromosome 16p13, in carbohydrate-deficient glycoprotein type I syndrome (Jaeken syndrome). 914 Apr 1

The congenital disorders of glycosylation (CDG) constitute a new group of recessively inherited metabolic disorders that are characterized biochemically by defective glycosylation of proteins. Several types have been identified. CDG-Ia, the most frequent type, is a multisystemic disorder affecting the nervous system and numerous organs including liver, kidney, heart, adipose tissue, bone, and genitalia. A phosphomannomutase (PMM) deficiency has been identified in CDG-Ia patients and numerous mutations in the PMM2 gene have been identified in patients with a PMM deficiency. We report on a French family with 3 affected sibs, with an unusual presentation of CDG-Ia, remarkable for 1) the neurological presentation of the disease, and 2) the dissociation between intermediate PMM activity in fibroblasts and a decreased PMM activity in leukocytes. This report shows that the diagnosis of CDG-Ia must be considered in patients with non-regressive early-onset encephalopathy with cerebellar atrophy, and that intermediate values of PMM activity in fibroblasts do not exclude the diagnosis of CDG-Ia.
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PMID:Neurological presentation of a congenital disorder of glycosylation CDG-Ia: implications for diagnosis and genetic counseling. 1134 37