Fukuda M N
La Jolla Cancer Research Foundation, CA 92037.
Baillieres Clin Haematol. 1993 Jun;6(2):493-511. doi: 10.1016/s0950-3536(05)80156-8.
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.
II型先天性红细胞生成异常性贫血（CDA II）是一种罕见的人类遗传性贫血，呈常染色体隐性遗传。CDA II也被称为先天性多核成红细胞增多症伴酸化血清溶血试验阳性（HEMPAS）。对CDA II红细胞膜的分析表明，带3糖蛋白糖基化不足。在通常附着于带3和带4.5糖蛋白的多乳糖胺碳水化合物中可见异常的糖基化模式。然而，多乳糖胺以糖脂的形式积累。因此，CDA II中的一个遗传因素似乎阻断了蛋白质受体的糖基化，并将这些碳水化合物转移到脂质受体上。对CDA II带3碳水化合物的结构分析鉴定出截短的杂合型寡糖，并表明高尔基体糖基化酶α-甘露糖苷酶II或N-乙酰氨基葡萄糖转移酶II在CDA II中存在缺陷。通过使用α-甘露糖苷酶II的cDNA探针，已鉴定出1例CDA II病例在编码α-甘露糖苷酶II的基因中存在缺陷。目前尚不清楚CDA II是糖基化缺陷的遗传异质性集合，还是在表型表达上遗传同质但明显异质。冷冻蚀刻电子显微镜和免疫电子显微镜显示，带3糖蛋白在CDA II红细胞膜中聚集。带3的异常分布可能导致膜组织不稳定。在CDA II成红细胞中，膜蛋白也可能糖基化不足且分布异常。当正常成红细胞在苦马豆素（α-甘露糖苷酶抑制剂）存在下进行体外培养时，成红细胞会变成多核。因此，α-甘露糖苷酶II的酶缺陷很可能导致包括多核在内的各种形态异常。由于编码糖基化酶的基因是管家基因，CDA II的酶缺陷不仅限于红细胞，肝细胞糖蛋白也存在异常糖基化。另一方面，有许多类型的细胞和组织似乎不受CDA II缺陷的影响。本文还讨论了CDA II红细胞特异性表现及其组织特异性的机制。
