Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0002871 (anemia)
 52,094 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Congenital dyserythropoietic anaemia Type II or HEMPAS (hereditary erythroblastic multinuclearity with positive acidified serum lysis test) is a rare genetic anaemia in humans, inherited in an autosomally recessive mode. Biochemical analyses of HEMPAS erythrocyte membranes suggested strongly that HEMPAS is caused by defective glycosylation of erythrocyte membrane glycoproteins. Most recently a HEMPAS case has been identified as being defective in the gene encoding Golgi alpha-mannosidase II by using cDNA probe of alpha-mannosidase II. At present, it is not clear whether HEMPAS is a genetically heterogenous collection of glycosylation deficiencies, as some HEMPAS cases showed a low level of N-acetylglucosaminyltransferase II. Abnormal glycosylation of serum glycoproteins and association of liver cirrhosis in HEMPAS patients indicate that HEMPAS disease is not restricted to erythroid cells. On the other hand, normal development of HEMPAS patients during embryonic stage strongly suggests the possibilities of fetal type isozyme in place of defective glycosylation enzyme.
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PMID:HEMPAS disease: genetic defect of glycosylation. 213 85

Congenital dyserythropoietic anemia type II, or hereditary erythroblastic multinuclearity with a positive acidified-serum-lysis test (HEMPAS), is a genetic anemia in humans inherited by an autosomally recessive mode. The enzyme defect in most HEMPAS patients has previously been proposed as a lowered activity of N-acetylglucosaminyltransferase II, resulting in a lack of polylactosamine on proteins and leading to the accumulation of polylactosaminyl lipids. A recent HEMPAS case, G.C., has now been analyzed by cell-surface labeling, fast-atom-bombardment mass spectrometry of glycopeptides, and activity assay of glycosylation enzymes. Significantly decreased glycosylation of polylactosaminoglycan proteins and incompletely processed asparagine-linked oligosaccharides were detected in the erythrocyte membranes of G.C. In contrast to the earlier studied HEMPAS cases, G.C. cells are normal in N-acetylglucosaminyltransferase II activity but are low in alpha-mannosidase II (alpha-ManII) activity. Northern (RNA) analysis of poly(A)+ mRNA from normal, G.C., and other unrelated HEMPAS cells all showed double bands at the 7.6-kilobase position, detected by an alpha-ManII cDNA probe, but expression of these bands in G.C. cells was substantially reduced (less than 10% of normal). In Southern analysis of G.C. and normal genomic DNA, the restriction fragment patterns detected by the alpha-ManII cDNA probe were indistinguishable. These results suggest that G.C. cells contain a mutation in alpha-ManII-encoding gene that results in inefficient expression of alpha-ManII mRNA, either through reduced transcription or message instability. This report demonstrates that HEMPAS is caused by a defective gene encoding an enzyme necessary for the synthesis of asparagine-linked oligosaccharides.
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PMID:Incomplete synthesis of N-glycans in congenital dyserythropoietic anemia type II caused by a defect in the gene encoding alpha-mannosidase II. 221 75

Congenital dyserythropoietic anemia type II or HEMPAS (hereditary erythroblastic multinuclearity with positive acidified serum lysis test) is a genetic anemia in humans caused by a glycosylation deficiency. Erythrocyte membrane glycoproteins, such as band 3 and band 4.5, which are normally glycosylated with polylactosamines lack these carbohydrates in HEMPAS. Polylactosamines accumulate as glycolipids in HEMPAS erythrocytes. Analysis of N-glycans from HEMPAS erythrocyte membranes revealed a series of incompletely processed N-glycan structures, indicating defective glycosylation at N-acetylglucosaminyltransferase II (GnT-II) and/or alpha-mannosidase II (MII) steps. Genetic analysis has identified two cases from England in which the MII gene is defective. Mutant mice in which the MII gene was inactivated by homologous recombination resulted in a HEMPAS-like phenotype. On the other hand, linkage analysis of HEMPAS cases from southern Italy excluded MII and GnT-II as the causative gene, but identified a gene on chromosome 20q11. HEMPAS is therefore genetically heterogeneous. Regardless of which gene is defective, HEMPAS is characterized by incomplete processing of N-glycans. The study of HEMPAS will identify hitherto unknown factors affecting N-glycan synthesis.
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PMID:HEMPAS. Hereditary erythroblastic multinuclearity with positive acidified serum lysis test. 1057 Oct 15