Pons R, Roig M, Riudor E, Ribes A, Briones P, Ortigosa L, Baldellou A, Gil-Gibernau J, Olesti M, Navarro C, Wanders R J
Child Neurology Unit, Vall d'Hebron University Hospital, Barcelona, Spain.
Pediatr Neurol. 1996 Apr;14(3):236-43. doi: 10.1016/0887-8994(96)00021-5.
Four patients with long-chain 3-hydroxyacyl-coenzyme A dehydrogenase deficiency are presented. Clinical onset in the form of acute encephalopathy occurred between the ages of 9 months and 3 years. The clinical course included recurrent metabolic crises in 4 patients, cardiac involvement and retinopathy in 3, and myopathy in 2. None had signs of peripheral neuropathy. Three patients died and one is currently well. Hypoketotic hypoglycemia with C6-C14 3-hydroxy-dicarboxylic aciduria during metabolic crises associated with decreased plasma carnitine levels was the main biochemical finding. Enzymologic studies disclosed long-chain 3-hydroxyacyl-coenzyme A dehydrogenase deficiency in all patients. Homozygosity for a G to C mutation at position 1528 in the encoding region of the enzyme was found in 2 patients. Histologic and electron microscopic studies of liver biopsy specimens revealed steatosis in 3 patients and mitochondrial abnormalities in 2. Skeletal muscle biopsies disclosed nonspecific degenerative changes in 2 patients and were normal in the remaining 2. Ultrastructural abnormalities in mitochondria were found in 3 patients. A review of the literature combined with the data from our series (total 22 patients) disclosed acute clinical onset in 77% of cases and subacute in 23%. In the combined series, the average age at onset was 11 months, family history was positive in 32% of patients and overall mortality was 50%. We describe the clinical spectrum of this disease and emphasize that, among patients with suspected beta-oxidation defects the finding of pigmentary retinopathy should lead to the suspicion of long-chain 3-hydroxyacyl-coenzyme A-dehydrogenase deficiency.
本文报告了4例长链3-羟基酰基辅酶A脱氢酶缺乏症患者。临床起病形式为急性脑病，发病年龄在9个月至3岁之间。临床病程包括4例患者反复出现代谢危机，3例有心脏受累和视网膜病变，2例有肌病。均无周围神经病变体征。3例患者死亡，1例目前情况良好。代谢危机期间出现低酮性低血糖伴C6 - C14 3-羟基二羧酸尿症，同时血浆肉碱水平降低，这是主要的生化发现。酶学研究显示所有患者均存在长链3-羟基酰基辅酶A脱氢酶缺乏。2例患者在该酶编码区第1528位存在G到C的突变纯合子。肝活检标本的组织学和电子显微镜研究显示，3例患者有脂肪变性，2例有线粒体异常。骨骼肌活检显示2例患者有非特异性退行性改变，其余2例正常。3例患者线粒体存在超微结构异常。结合文献复习及我们系列研究的数据（共22例患者）发现，77%的病例临床急性起病，23%为亚急性起病。在综合系列研究中，平均发病年龄为11个月，32%的患者有家族史阳性，总体死亡率为50%。我们描述了该病的临床谱，并强调在疑似β氧化缺陷的患者中，色素性视网膜病变的发现应引起对长链3-羟基酰基辅酶A脱氢酶缺乏症的怀疑。
