Long-chain hydroxydicarboxylic aciduria, carnitine depletion and acetaminophen exposure
Long-chain hydroxydicarboxylic aciduria, carnitine depletion and acetaminophen exposure
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DOI：
10.1023/a:1005630218986
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发表时间：
2000-03-01
影响因子：
4.2
通讯作者：
Pollitt, RJ
中科院分区：
文献类型：
--
作者：
Nowaczyk, MJM;Whelan, D;Pollitt, RJ
长链3-羟酰辅酶A脱氢酶缺乏（LCHADD）（McKusick 600890）可能在并发疾病期间表现为低酮性低血糖、脑病、肝功能障碍和特征性尿有机酸排泄模式。我们报告一个11个月大的男孩谁提出了脑病和急性肝功能障碍后，暴露于对乙酰氨基酚（扑热息痛）。他的尿有机酸排泄模式是典型的LCHADD，但他的脂肪酸氧化酶测定是正常的。病人，以前很好，表现为强直阵挛性癫痫发作，脑病和急性肝衰竭后发热性疾病。他接受了15 mg/kg对乙酰氨基酚，每4 h一次，共150 mg/kg/24 h（剂量限值65 mg/kg/24 h）。患者出现肝肿大，入院第二天观察到转氨酶显著升高（AST 2460 IU/L，ALT 1192 IU/L;两者均正常值<40），随后出现低血糖（葡萄糖2.2 mmol/L）和持续性脑病。从急性疾病期间获得的尿液中分析的有机酸显示排泄了中等量的酮体（3-羟基丁酸、乙酰乙酸）、中等量的己二酸、辛二酸和癸二酸以及3-羟基癸二酸、3-羟基十二烷二酸、3-羟基十四烷二酸和少量的3-羟基十四烷二烯二酸、不饱和癸二酸和不饱和辛二酸。用稳定同位素稀释法测得的尿酰基甘氨酸排泄量正常。在发病第5天，他出现肝转氨酶（ALT [8000和ALT [6000 IU/L]）、凝血功能障碍（PT 17.2; PTT 60.2）和高氨血症（200 kmol/L;正常\40）大幅升高。总肉毒碱为31.4 kmol/L（正常值48 - 72 kmol/L），游离肉毒碱为21.9 kmol/L（正常值35 - 50 kmol/L）。血浆甲胎蛋白为323 kmol/L（正常值为0 - 10 kmol/L）。在发病第10天，经皮肝活检显示肝细胞肿胀，偶见脂肪滴，所有小叶中心区3区坏死。电子显微镜检查显示线粒体和过氧化物酶体正常。由于尿有机酸排泄模式和肝功能障碍的严重程度，考虑LCHADD的临床诊断。在第11天开始用低脂肪、中链甘油三酯油补充的饮食和口服L-肉毒碱（100 mg/kg/天）治疗。肝功能改善，第16天出院回家。然而，使用[9，10 - 3H]棕榈酸作为底物通过氚释放测定的培养的皮肤成纤维细胞中脂肪酸b-氧化的测定是正常的，通过LCHADD突变14CO2的DNA测定释放测定的[1 - 14C]-丁酸的氧化也是正常的。1528G [C（E474Q）为阴性。
Long-chain 3-hydroxyacyl-CoA dehydrogenase de-ciency (LCHADD)(McKusick 600890) may present with hypoketotic hypoglycaemia, encephalopathy, liver dysfunction and a characteristic urine organic acid excretion pattern during intercurrent illness. We report an 11-month-old boy who presented with encephalopathy and acute liver dysfunction following exposure to acetaminophen (paracetamol). His urinary organic acid excretion pattern was typical of LCHADD, but his fatty acid oxidation enzyme assays were normal.The patient, previously well, presented with a tonic-clonic seizure, encephalopathy and acute liver failure following a febrile illness. He had received 15 mg/kg of acetaminophen every 4 h for a total of 150 mg/kg per 24 h (dose limit 65 mg/kg/24 h). He developed hepatomegaly, and marked rises in transaminases (AST 2460 IU/L, ALT 1192 IU/L; normal values\40 for both) were observed on the second day of admission followed by hypoglycaemia (glucose 2.2 mmol/L), and persistent encephalopathy. Organic acids analysed from urine obtained during the acute illness showed excretion of moderate amounts of ketone bodies (3-hydroxybutyrate, acetoacetate), moderate amounts of adipate, suberate and sebacate, as well as 3-hydroxysebacic, 3-hydroxydodecanedioic, 3-hydroxytetradecanedioic, and small amounts of 3hydroxytetradecadienedioic, unsaturated sebacic, and unsaturated suberic acids. The excretion of urinary acylglycines, measured by a stable-isotope dilution method, was normal. On day 5 of illness, he had massive elevation of hepatic aminotransferases (ALT [8000 and ALT [6000 IU/L), coagulopathy (PT 17.2; PTT 60.2), and hyperammonaemia (200 kmol/L; normal\40). Total carnitine was 31.4 kmol/L (normal 48" 72 kmol/L) and free carnitine was 21.9 (normal 35" 50 kmol/L). Plasma a-fetoprotein was 323 kmol/L (normal 0" 10 kmol/L). On day 10 of illness, a percutaneous liver biopsy showed swollen hepatocytes with occasional fat droplets, and zone 3 necrosis in all centrilobular areas. Electron microscopy showed normal mitochondria and peroxisomes. A clinical diagnosis of LCHADD was considered because of the urinary organic acid excretion pattern and the severity of liver dysfunction. Treatment with a low-fat, medium-chain triglyceride oilsupplemented diet and oral L-carnitine (100 mg/kg per day) was begun on day 11. Liver function improved and he was discharged home on day 16. However, assays of fatty acid b-oxidation in cultured skin-broblasts determined by tritium release using [9, 10-3H] palmitic acid as substrate were normal, as was oxidation of [1-14C]-butyrate, determined by release of DNA assay for the LCHADD mutation 14CO2. 1528G [C (E474Q) was negative.