Pollitt R J
Neonatal Screening Laboratory, Children's Hospital, Sheffield, UK.
J Inherit Metab Dis. 1995;18(4):473-90. doi: 10.1007/BF00710058.
The oxidation of long-chain fatty acids requires a series of enzymes which are located in or on the mitochondrial membranes. These include carnitine palmitoyltransferases I and II, a carnitine-acylcarnitine translocase and, newly discovered, very long-chain acyl-CoA dehydrogenase and the mitochondrial trifunctional protein. These last two chain-shorten acyl-CoA esters to the point where they can be transferred to the more soluble medium- and short-chain-specific enzymes within the mitochondrial matrix. The disorders of long-chain fatty acid oxidation show a rather similar range of clinical and biochemical features, though with different emphasis in the different conditions. Patients with severe defects usually present early with acute attacks of hypoketotic hypoglycaemia and impaired liver function, or with cardiomyopathy or cardiac arrhythmia. In milder variants, skeletal myopathy with intermittent myoglobinuria develops later in life. 3-Hydroxyacyl-CoA dehydrogenase deficiency is unusual in producing peripheral neuropathy and retinitis pigmentosa. Treatment is based on the avoidance of fasting and replacement of normal dietary fat by medium-chain triglyceride, the medium-chain fatty acids entering the mitochondria in a carnitine-independent manner and bypassing the long-chain part of the spiral. Diagnosis must ultimately be based on direct assay of the enzyme involved, but preliminary indicators may come from determination of carnitine and intermediate metabolites in plasma, urinary organic acid profiling, and radioisotopic screening assays with lymphocytes or cultured fibroblasts.
长链脂肪酸的氧化需要一系列位于线粒体膜内或膜上的酶。这些酶包括肉碱棕榈酰转移酶I和II、一种肉碱 - 脂酰肉碱转位酶,以及新发现的极长链酰基辅酶A脱氢酶和线粒体三功能蛋白。后两种酶将酰基辅酶A酯链缩短至一定程度,使它们能够转移到线粒体基质中更易溶解的中链和短链特异性酶作用。长链脂肪酸氧化障碍表现出相当相似的一系列临床和生化特征,尽管在不同情况下侧重点有所不同。严重缺陷的患者通常早期出现低酮性低血糖急性发作和肝功能受损,或出现心肌病或心律失常。在症状较轻的变体中,骨骼肌病伴间歇性肌红蛋白尿在生命后期出现。3 - 羟酰基辅酶A脱氢酶缺乏症在导致周围神经病变和色素性视网膜炎方面较为罕见。治疗方法是避免禁食,并用中链甘油三酯替代正常饮食脂肪,中链脂肪酸以不依赖肉碱的方式进入线粒体,绕过螺旋的长链部分。诊断最终必须基于对相关酶的直接检测,但初步指标可能来自血浆中肉碱和中间代谢物的测定、尿有机酸谱分析以及淋巴细胞或培养成纤维细胞的放射性同位素筛查检测。