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At least 19 recordsLinked to original sources
PubMed1984

Defect in glycosylation of erythrocyte membrane proteins in congenital dyserythropoietic anaemia type II (HEMPAS).

Congenital dyserythropoietic anaemia type II (HEMPAS) is a hereditary disease believed to be caused by a membrane abnormality of erythroid cells. Since the molecular basis of this membrane abnormality has not yet been defined, membrane glycoproteins of HEMPAS erythrocytes were analysed by cell surface labelling and endo-beta-galactosidase digestion in this study. HEMPAS erythrocytes showed an abnormal glycoprotein profile when cells were labelled by the galactose oxidase/NaB[3H]4 method; Band 3 and Band 4.5 glycoproteins in HEMPAS are labelled but with less intensity although normally these proteins are the major components revealed by the same method. Instead, in HEMPAS, labelled lactosaminoglycans were found as a lower molecular weight glycoconjugate (HEMPAS glycan). HEMPAS glycan was characterized by micelle formation, a monomer molecular weight of 4000, susceptibility to endo-beta-galactosidase and resistance to protease. These characteristics suggest that HEMPAS glycan has the nature of macroglycolipid. Proteins of Band 3 and the glucose transport protein (a component of Band 4.5), which were detected by antibodies showed a slightly decreased molecular weight in HEMPAS erythrocytes compared to those from normal erythrocytes, which was consistent with the decreased glycosylation of these proteins. The results indicate that anomalies in glycosylation occurred specifically in lactosaminoglycan glycoproteins of HEMPAS erythrocytes.

Anemia, Dyserythropoietic, Congenital↗
PubMed1999

HEMPAS. Hereditary erythroblastic multinuclearity with positive acidified serum lysis test.

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.

Anemia, Dyserythropoietic, Congenital↗
PubMed1990

HEMPAS disease: genetic defect of glycosylation.

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.

Anemia, Dyserythropoietic, Congenital↗
PubMed1992

Incompletely processed N-glycans of serum glycoproteins in congenital dyserythropoietic anaemia type II (HEMPAS).

Congenital dyserythropoietic anaemia type II, or HEMPAS (hereditary erythroblastic multinuclearity with positive acidified serum lysis test) is a genetic disease caused by membrane disorganization of erythroid cells. The primary defect of this disease lies in the gene encoding enzyme(s) which is responsible for the biosynthesis of Asn-linked oligosaccharides chains of glycoproteins (Fukuda et al, 1990). In order to know whether this gene defect affects the glycosylation in the cells other than the erythroid cells, the carbohydrate structures of the transferrin isolated from the sera of HEMPAS patients were analysed. Fast atom bombardment mass spectrometry analysis showed the presence of high mannose type and hybrid type oligosaccharides in the HEMPAS transferrin which is in contrast to the complex-type oligosaccharides found in the normal transferrin. The results strongly suggest that biosynthesis of Asn-linked oligosaccharide chains in HEMPAS hepatocytes is disturbed. As a result, the serum glycoproteins with incompletely processed carbohydrates are circulating in the plasma in HEMPAS patients, but they must have been absorbed by the cells in the liver and the reticuloendothelial cells. Upon intravenous infusion into rats, as much as 30% of the HEMPAS transferrin was cleared from the plasma circulation. The majority of the HEMPAS transferrins was taken up by the liver, and transferrin was distributed both in the hepatocytes and the Kupffer cells. The presence of enormous amounts of aberrantly glycosylated serum glycoproteins may lead to the liver cirrhosis and secondary tissue siderosis seen in HEMPAS patients.

Adult↗
PubMed1998

Structural and functional consequences of an N-glycosylation mutation (HEMPAS) affecting human erythrocyte membrane glycoproteins.

Band 3, the human erythrocyte anion exchanger (AE1), and the glucose transporter (GLUT1) proteins each contain a single site of N-glycosylation that is heterogeneously glycosylated. Lectin binding and enzymatic deglycosylation assays showed that the polylactosaminyl oligosaccharide structure of these glycoproteins was altered to a high mannose or hybrid glycan form in three patients with hereditary erythroblastic multinuclearity, with a positive acidified-serum lysis test (HEMPAS). Offspring from one of the HEMPAS patients had intermediate levels of polylactosaminyl oligosaccharide associated with AE1 and GLUT1, suggesting they may have been heterozygous for the genetic defect. The array of polylactosaminyl-containing glycoproteins present in EBV-transformed lymphoblasts derived from fresh blood of HEMPAS patients was similar to control lymphoblasts. HEMPAS lymphoblasts do not therefore express the defect in polylactosamine synthesis found in erythroid cells, indicating that lymphoid cells are not deficient in the processing enzymes or contain an alternative oligosaccharide processing pathway. Purified HEMPAS band 3 had an unaltered oligomeric structure but dimers aggregated more rapidly in detergent solution than normal band 3. The altered oligosaccharide structure did not affect the sensitivity of band 3 to proteolytic digestion in intact red cells but a greater amount of HEMPAS band 3 was associated with the cytoskeleton. The transport activities of AE1 and GLUT1 in HEMPAS erythrocytes were similar to those in normal controls. This shows that the HEMPAS glycosylation defect does not impair the functional accumulation of these two important erythrocyte membrane transporters even though it produces subtle structural changes in band 3 that result in its increased cytoskeletal interaction and self association in detergent solution.

Anemia, Dyserythropoietic, Congenital↗
PubMed1994

Aberrant regulation of complement by the erythrocytes of hereditary erythroblastic multinuclearity with a positive acidified serum lysis test (HEMPAS).

Susceptibility to hemolysis in acidified serum is a pathognomonic feature of hereditary erythroblastic multinuclearity with a positive acidified serum lysis test (HEMPAS, congenital dyserythropoietic anemia type II). The purpose of the studies reported herein was to determine if aberrant regulation of complement contributes to the susceptibility of HEMPAS erythrocytes to acidified serum lysis. The results of these experiments have demonstrated that regulation of both the C3 convertase of the alternative pathway and the membrane attack complex of complement by HEMPAS erythrocytes is aberrant. However, these abnormalities are not a consequence of quantitative or functional deficiencies of the erythrocyte complement-regulatory proteins, decay accelerating factor (DAF, CD55), or membrane inhibitor of reactive lysis (MIRL, CD59). Our recent studies have shown that glycophorin A (GPA), the major erythrocyte sialoglycoprotein is a complement regulatory protein. Analysis by radioimmunoprecipitation suggested that GPA on HEMPAS erythrocytes is abnormally glycosylated. Further analysis indicated that the abnormality involves the O-linked oligosaccharide moiety. Together, these studies show that complement regulation by HEMPAS erythrocytes is abnormal and that constituents other than DAF and MIRL participate in controlling complement activation on the erythrocyte membrane. Additionally, these studies suggest that the glycosylation defect that is characteristic of HEMPAS involves GPA.

Anemia, Dyserythropoietic, Congenital↗
PubMed1994

Polylactosamines are not obligate receptors for invasion of Plasmodium falciparum malaria as shown in HEMPAS variant II-gal- erythrocytes.

A HEMPAS (hereditary erythroblastic multinuclearity with positive acidified serum test) erythrocyte, atypical Variant II (referred to herein as Variant II-gal-), lacking long-chain polylactosamine on both glycoproteins (Band 3 and 4.5) and glycosphingolipids, was characterized by the carbohydrate profile of the erythrocyte membrane according to Fukuda et al. (Blood, 73, 1331-1339, 1989). Two laboratories previously reported that polylactosamine isolated from the erythrocyte protein Band 3 inhibited invasion of red blood cells by Plasmodium falciparum in malarial culture, suggesting a role for this carbohydrate in adhesion of the parasite. Therefore, HEMPAS erythrocyte Variant II-gal- presented a unique opportunity to further examine this premise. Freshly drawn blood samples (normal and HEMPAS Variant II-gal-) were separately incubated with P. falciparum from mannitol-synchronized cultures. The parasite was found to invade HEMPAS Variant II-gal- erythrocytes at a 30% lower rate through two life cycles, as shown by microscopic evaluation of invasion and by [3H]hypoxanthine incorporation into parasite. This observation, along with the published fact that glycophorin-deficient MkMk cells are also infectable, but at a lower rate, indicates that neither sialoglycoproteins nor polylactosamines are an obligate adhesive ligand for P. falciparum, although the possibility remains that either may still contribute to adhesive events during infection.

Amino Sugars↗
PubMed1976

[Polyagglutinability due to Hempas antigen].

A new antigen has been recently discoverd in patients with congenital dyserythropoietic anemia type II. The acronyme Hempas was proposed for this disease as a remind of the main morphological feature of erythroblasts (hereditary erythroblastic multinuclearity) and the characteristic serological findings (positive acidified serum test). The patients red cells are agglutinated and lysed by an IgM cold reacting antibody present in the serum of most normal subjects and not previously recognized. This behaviour is thus reminding of cells carrying antigens such as T, Tn, Cad or acquired B. As for T and Tn cells, sialic acid and electrophoretic mobility are reduced, but in contrast, agglutinability of Hempas cells is enhanced by enzyme treatment. Agglutination by anti H and anti Pr specific reagents is reduced. I and mainly i activity are strongly increased. The relationship between the membrane abnormalities of Hempas red cells and the failure of normoblasts to divide their cytoplasm i still largely unknown.

Complement System Proteins↗
PubMed1979

Morphological Abnormalities in cultured erythroid colonies (BFU-E) from the blood of two patients with HEMPAS.

The results of cytological and ultrastructural analysis of erythroid burst colonies derived from the peripheral blood of two patients with HEMPAS have been compared to those obtained in normal controls. Using the plasma clot technique, in studies on 10 subjects we confirmed that most of the colonies consisted or erythroblasts with a synchronous and normal maturation involving a wave of nuclear extrusion at day 13. In contrast, the majority of well-haemoglobinized colonies from HEMPAS consisted of numerous bi- or multinucleated erythroblasts displaying the supplementary double membrane beneath their plasma membrane. This excessive membrane may be present as a continuous or fragmented structure in different erythroblasts from the same colony. These findings suggest that the progeny derived from one BFU-E may vary considerably in their morphological defects. Furthermore, one third of the packed colonies appeared to be formed by non-haemoglobinized cells which were clearly identified by electron microscopy as very early erythroblasts. These cells were unable to mature and subsequently lysed. Thus dyserythropoiesis occurred in culture both at early and late stages of maturation. These studies clearly demonstrate that HEMPAS is a disorder resulting from defective erythroid committed cells.

Adult↗
PubMed1995

Carbohydrate-deficient glycoprotein syndrome type II. An autosomal recessive N-acetylglucosaminyltransferase II deficiency different from typical hereditary erythroblastic multinuclearity, with a positive acidified-serum lysis test (HEMPAS).

Carbohydrate-deficient glycoprotein syndromes (CDGS) are a family of multisystemic congenital diseases resulting in underglycosylated glycoproteins, suggesting defective N-glycan assembly. Fibroblast extracts from two patients with a recently described variant of this disease (CDGS type II) have previously been shown to have over 98% reduced activity of UDP-GlcNAc:alpha-6-D-mannoside beta-1,2-N-acetylglucosaminyltransferase II [GlcNAc-TII; Jaeken, J., Schachter, H., Carchon, H., De Cock, P., Coddeville, B. & Spik, G. (1994) Arch. Dis. Childhood 71, 123-127]. We show in this paper that mononuclear cell extracts from one of these CDGS type-II patients have no detectable GlcNAc-TII activity and that similar extracts from 12 blood relatives of the patient, including his father, mother and brother, have GlcNAc-TII levels 32-67% that of normal levels (average 50.1% +/- 10.7% SD), consistent with an autosomal recessive disease. The poly(N-acetyllactosamine) content of erythrocyte membrane glycoproteins bands 3 and 4.5 of this CDGS patient were estimated, by tomato lectin blotting, to be reduced by 50% relative to samples obtained from blood relatives and normal controls. Similar to patients with hereditary erythroblastic multinuclearity with a positive acidified-serum lysis test (HEMPAS), erythrocyte membrane glycoproteins in the CDGS patient have increased reactivities with concanavalin A, demonstrating the presence of hybrid or oligomannose carbohydrate structures. However, bands 3 and 4.5 in HEMPAS erythrocytes have almost complete lack of poly(N-acetyllactosamine). Furthermore, CDGS type-II patients have a totally different clinical presentation and their erythrocytes do not show the serology typical of HEMPAS, suggesting that the genetic lesions responsible for these two diseases are possibly different.

Adolescent↗
PubMed1976

The action of seed and other reagents on HEMPAS erythrocytes.

Erythrocytes of a patient with hereditary erythroblastic multinuclearity with a positive acidified serum test (HEMPAS) were tested with many seed extracts and various other reagents. Serological evidence of membrane abnormality was confirmed. Various anti-H reagents reacted relatively poorly with HEMPAS cells. HEMPAS cells have both enhanced i and depressed H antigens. A brief note on a 'new' anti-H lectin (Cytisus glabrescens) is provided.

Anemia↗
PubMed1980

Cytochemical changes induced by apholate, tepa and hempa during vitellogenesis in Locusta migratoria.

Proteins (--SS, --SH, and NH2 groups; tyrosine, tryptophan and arginine), DNA, phospholipids and triglycerides showed a progressive decline in the oocytes of Locusta migratoria with increase in doses of apholate, tepa and hempa. Carbohydrates showed a decline only after higher doses of apholate and tepa whereas they were not affected at all with hempa. The pyroninophilia due to RNA in the oocytes decreased in the ooplasm of oocytes slightly, but increased in the cytoplasm and nucleoplasm of follicular epithelial cells with all the chemosterilants. The follicular epithelial cells degenerated in the mature oocytes, and yolk formation was inhibited.

Animals↗
PubMed1978

Cytogenetic and other effects of the chemosterilants tepa, metepa, apholate an hempa in insects (a review).

A review of the literature revealed that the chemosterilants tepa (tris(1-aziridinyl)phosphine oxide), metepa (tris(2-methyl-1-aziridinyl) phosphineoxide), apholate (2,2,4,4,6,6-hexakis(1-aziridinyl)-2,2,4,4,6,6-hexahydro-1,3,5,2,4,6-triazatriphosphorine), and hempa (hexamethylmelamine) affected both reproductive and somatic tissues in over 65 species of insects. The effects were cytological, physiological, and genetic and varied from slight to severe. In some cases the deleterious effects may have been species-specific, but in general, they appeared to be dose-dependent. More than 150 publications are cited.

Animals↗
PubMed2002

Piebaldism associated with congenital dyserythropoietic anemia type II (HEMPAS).

Congenital dyserythropoietic anemias (CDAs) are a group of relatively rare inherited anemias. They are characterized by ineffective erythropoiesis and classified as three major groups and a number of variants. CDA type II, also known as hereditary erythroblastic multinuclearity with a positive acidified serum test (HEMPAS), is the most frequent one. A number of associations with CDA II have been reported, although each described only one or a few patients. Here we presented a piebald woman with vaginal atresia who was tested for anemia and diagnosed as CDA type II. Piebaldism and anemia association were previously described in the mouse. Our case was the first that shows the features of both piebaldism and CDA in the same patient. This association may suggest a stem cell defect to cause both hematopoietic and cutaneous manifestations.

Adult↗
PubMed1993

Congenital dyserythropoietic anaemia type II (HEMPAS) and its molecular basis.

Congenital dyserythropoietic anaemia type II (CDA II) is a rare genetic anaemia in humans, inherited in an autosomally recessive mode. CDA II is also called HEMPAS as this disease is characterized by hereditary erythroblastic multinuclearity with positive acidified serum lysis test. Analyses of CDA II erythrocyte membranes showed that the band 3 glycoprotein is underglycosylated. An aberrant glycosylation pattern is seen in the polylactosamine carbohydrates which are normally attached to the band 3 and band 4.5 glycoproteins. The polylactosamines are, however, accumulated in the form of glycolipids. Therefore a genetic factor in CDA II appears to block the glycosylation of protein acceptors and shift these carbohydrates to the lipid acceptors. Structural analysis of CDA II band 3 carbohydrates identified truncated hybrid-type oligosaccharides and suggests that the Golgi glycosylation enzyme(s), alpha-mannosidase II or N-acetylglycosaminyltransferase II is defective in CDA II. By using a cDNA probe for alpha-mannosidase II, one CDA II case has been identified as being defective in the gene encoding alpha-mannosidase II. At present, it is not clear whether CDA II is a genetically heterogenous collection of glycosylation deficiencies, or genetically homogenous but apparently heterogenous in phenotype expression. Freeze-fracture electron microscopy and immunoelectron microscopy revealed that the band 3 glycoproteins are clustered in CDA II erythrocyte membranes. The abnormal distribution of band 3 might cause an unstable membrane organization. In CDA II erythroblasts, the membrane proteins might also be underglycosylated and abnormally distributed. When normal erythroblasts were cultured in vitro in the presence of swainsonine (alpha-mannosidase inhibitor) the erythroblasts became multinucleared. It is, therefore, quite possible that the enzymic defect of alpha-mannosidase II could cause various morphological anomalies including multinuclearity. Because the genes encoding glycosylation enzymes are housekeeping genes, the enzyme defect of CDA II is not restricted to erythroid cells and there is also an abnormal glycosylation of hepatocyte glycoproteins. On the other hand, there are many types of cells and tissues which appear not to be affected by the CDA II defect. A mechanism for the erythroid-specific manifestation of CDA II and its tissue specificity are also discussed.

Anemia, Dyserythropoietic, Congenital↗
PubMed1982

Normal serum ferritin levels in a patient with HEMPAS syndrome and iron overload.

Serum ferritin levels in a patient with HEMPAS syndrome (hereditary erythroblastic multinuclearity associated with positive acidified serum test) were correlated with body iron stores directly measured on spleen and liver biopsy specimens as well as by quantitative serial phlebotomy. Normal serum ferritin concentrations were found in the presence of a moderate excess in iron stores (approximately 6-12 times normal). They temporarily increased after transfusion and splenectomy with a prompt return to the normal range. As repeated phlebotomies over a period of nine months depleted the excess iron stores, the serum ferritin ultimately decreased to a subnormal concentration. The serum ferritin concentration was not a reliable index of increased body iron stores in this iron overloaded patient, but did reflect their depletion by serial phlebotomy.

Anemia, Dyserythropoietic, Congenital↗