Wang S S, Fernhoff P M, Hannon W H, Khoury M J
Epidemic Intelligence Service, Division of Applied Public Health Training, Epidemiology Program Office, Centers for Disease Control and Prevention, Atlanta, Georgia, USA.
Genet Med. 1999 Nov-Dec;1(7):332-9. doi: 10.1097/00125817-199911000-00004.
Medium chain acyl-CoA dehydrogenase (MCAD) is a tetrameric flavoprotein essential for the beta-oxidation of medium chain fatty acids. MCAD deficiency (MCADD) is an inherited error of fatty acid metabolism. The gene for MCAD is located on chromosome one (1p31). One variant of the MCAD gene, G985A, a point mutation causing a change from lysine to glutamate at position 304 (K304E) in the mature MCAD protein, has been found in 90% of the alleles in MCADD patients identified retrospectively. There is a high frequency of MCADD among people of Northern European descent, which is believed to be due to a founder effect. MCADD is inherited in an autosomal recessive manner. Of patients clinically diagnosed with MCADD, 81% who have been identified retrospectively are homozygous for K304E, and 18% are compound heterozygotes for K304E. Clinical data on the probability of clinical disease indicates that MCADD patients are at risk for the following outcomes: hypoglycemia, vomiting, lethargy, encephalopathy, respiratory arrest, hepatomegaly, seizures, apnea, cardiac arrest, coma, and sudden and unexpected death. Long-term outcomes include developmental and behavioral disability, chronic muscle weakness, failure to thrive, cerebral palsy, and attention deficit disorder (ADD). Differences in clinical disease specific to allelic variants have not been documented. Factors that may increase risk for disease onset or modify disease severity are age when the first episode occurred, fasting, and presence of infection. Acute attacks must be treated immediately with appropriate intravenous doses of glucose. For those diagnosed, long-term management of the disease includes preventing stress caused by fasting and maintaining a high-carbohydrate, reduced-fat diet, and carnitine supplementation. Hospitalization costs attributable to morbidity and mortality from MCADD are unknown; MCADD is not a diagnosis in the International Classification of Disease, 10th Revision (ICD-10) codebook. Furthermore, the penetrance of the MCAD genotypes is unknown; there appears to be a substantial number of asymptomatic MCADD individuals and some uncertainty regarding which individuals will manifest symptoms and which individuals will remain asymptomatic. Several technologies are available to detect MCADD. Diagnostic technologies include DNA-based tests for K304E mutations using the polymerase chain reaction (PCR), and the detection of abnormal metabolites in urine. Screening technologies include tandem mass spectrometry (MS/MS), which detects abnormal metabolites mostly in blood. State programs are beginning to offer screening in newborns for MCADD using MS/MS. In addition, a private company currently offers voluntary supplemental newborn screening for MCADD to birthing centers.
中链酰基辅酶A脱氢酶（MCAD）是一种四聚体黄素蛋白，对中链脂肪酸的β氧化至关重要。MCAD缺乏症（MCADD）是一种脂肪酸代谢的遗传性疾病。MCAD基因位于1号染色体（1p31）上。MCAD基因的一种变体，即G985A，是一种点突变，导致成熟MCAD蛋白第304位的赖氨酸变为谷氨酸（K304E），在回顾性鉴定的MCADD患者中，90%的等位基因中发现了这种突变。在北欧血统人群中，MCADD的发病率很高，这被认为是由于奠基者效应。MCADD以常染色体隐性方式遗传。在临床诊断为MCADD的患者中，回顾性鉴定出的患者中81%为K304E纯合子，18%为K304E复合杂合子。关于临床疾病发生概率的临床数据表明，MCADD患者有以下风险：低血糖、呕吐、嗜睡、脑病、呼吸骤停、肝肿大、癫痫发作、呼吸暂停、心脏骤停、昏迷以及突然意外死亡。长期后果包括发育和行为障碍、慢性肌肉无力、发育不良、脑瘫和注意力缺陷障碍（ADD）。尚未记录等位基因变体特有的临床疾病差异。可能增加疾病发作风险或改变疾病严重程度的因素包括首次发作时的年龄、禁食和感染情况。急性发作必须立即用适当静脉剂量的葡萄糖进行治疗。对于已确诊的患者，该疾病的长期管理包括预防禁食引起的应激、维持高碳水化合物、低脂饮食以及补充肉碱。因MCADD的发病率和死亡率导致的住院费用尚不清楚；MCADD不在《国际疾病分类第10版》（ICD - 10）编码手册中。此外，MCAD基因型的外显率尚不清楚；似乎有大量无症状的MCADD个体，对于哪些个体将出现症状以及哪些个体将保持无症状存在一些不确定性。有几种技术可用于检测MCADD。诊断技术包括使用聚合酶链反应（PCR）对K304E突变进行基于DNA的检测，以及检测尿液中的异常代谢产物。筛查技术包括串联质谱（MS/MS），其主要检测血液中的异常代谢产物。各州项目开始使用MS/MS对新生儿进行MCADD筛查。此外，一家私人公司目前向分娩中心提供自愿性补充新生儿MCADD筛查。
