Zia A, Kolodny E H, Pastores G M
Department of Pediatrics and Clinical Genetics at Columbia University Medical Center, Morgan Stanley Children's Hospital, New York, NY, USA.
J Inherit Metab Dis. 2007 Oct;30(5):817. doi: 10.1007/s10545-007-0582-2. Epub 2007 May 19.
Very long-chain acyl-CoA dehydrogenase (VLCAD) catalyses the initial step of mitochondrial beta-oxidation of long-chain fatty acids with a chain length of 14 to 20 carbons. Deficiency of VLCAD activity has been associated with a range of phenotypes, including a severe lethal form presenting in the infantile period and a milder variant with onset in childhood. Varying rates of residual enzyme activity partly explain the heterogeneity in presentations. Here we report the course of disease in a pair of monozygotic twin sisters who were diagnosed in their late forties during an evaluation for rhabdomyolysis and fatigue. Interestingly, the patients' complaints were most severe during puberty and declined significantly after the menopause. The basis for this observation is uncertain, but may be related to hormonally-mediated changes in lipid metabolism that may occur at these times. As metabolic decompensation can be associated with significant morbidity, timely diagnosis of VLCAD deficiency is important. The introduction of appropriate dietary measures (i.e. avoidance of fasting, long-chain fat restriction and supplementation with medium-chain triglycerides) greatly reduces the likelihood of complications.
极长链酰基辅酶A脱氢酶（VLCAD）催化超长链脂肪酸（碳链长度为14至20个碳）线粒体β-氧化的起始步骤。VLCAD活性缺乏与一系列表型相关，包括婴儿期出现的严重致死形式和儿童期起病的较轻变异型。残余酶活性的不同速率部分解释了临床表现的异质性。在此，我们报告一对同卵双胞胎姐妹的病程，她们在40多岁因横纹肌溶解和疲劳接受评估时被诊断。有趣的是，患者的症状在青春期最为严重，绝经后显著减轻。这一观察结果的依据尚不确定，但可能与这些时期可能发生的激素介导的脂质代谢变化有关。由于代谢失代偿可能与严重发病相关，及时诊断VLCAD缺乏很重要。采取适当的饮食措施（即避免禁食、限制长链脂肪并补充中链甘油三酯）可大大降低并发症的可能性。
