DEFECTIVE LYSOSOMAL RELEASE OF VITAMIN-B12 (CB1F) - A HEREDITARY COBALAMIN METABOLIC DISORDER ASSOCIATED WITH SUDDEN-DEATH
DEFECTIVE LYSOSOMAL RELEASE OF VITAMIN-B12 (CB1F) - A HEREDITARY COBALAMIN METABOLIC DISORDER ASSOCIATED WITH SUDDEN-DEATH
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DOI：
10.1002/ajmg.1320330431
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发表时间：
1989-08-01
期刊：
影响因子：
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通讯作者：
ROSENBLATT, DS
中科院分区：
文献类型：
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作者：
SHIH, VE;AXEL, SM;ROSENBLATT, DS
在这里，我们报告一个女孩谁提出了未能茁壮成长，发育迟缓，轻微的面部异常，口腔炎，皮疹，巨红细胞增多症，轻度同型半胱氨酸血症（尿），甲基丙二酸血症（尿）。成纤维细胞研究显示细胞内钴胺素（维生素B12）代谢异常。从[14 C]丙酸和[14 C]甲基四氢叶酸到TCA沉淀大分子中的14 C掺入减少分别反映了腺苷钴胺素和甲基钴胺素的合成减少。cbIF突变的诊断是通过证明成纤维细胞中未代谢的游离氰钴胺的积累和缺乏与来自唯一其他已知cb1F患者的成纤维细胞的遗传互补来建立的。缺陷在于内吞钴胺素的溶酶体释放。服用羟钴胺素可改善临床和生化指标，但在5个月大时发生猝死。脑病理改变的消失提示早期治疗可预防钴胺素辅因子缺乏症的神经系统并发症。
Here we report on a girl who presented with failure to thrive, developmental delay, minor facial anomalies, stomatitis, skin rashes, macrocytosis, mild homocystinemia-(uria), and methylmalonic acidemia(uria). Fibroblast studies showed abnormal intracellular cobalamin (vitamin B12) metabolism. Reduced incorporation of 14C from [14C] propionate and [14C] methyltetrahydrofolate into TCA-precipitable macromolecules reflected decreased synthesis of adenosylcobalamin and methylcobalamin respectively. The diagnosis of cbIF mutation was established by demonstrating the accumulation of unmetabolized free cyanocobalamin in fibrioblasts and by lack of genetic complementation with fibroblasts from the only other known cb1F patients. The defect is in the lysosomal release of endocytosed cobalamin. Administration of hydroxocobalamin resulted in clinical and biochemical improvement but sudden death occurred at age 5 months. The absence of brain pathological changes suggests that early treatment may prevent the neurological complications in cobalamin cofactor deficiency.