Division of Genetics, Children's Hospital Boston, Boston, MA 02115, USA.
Mol Genet Metab. 2010 Sep;101(1):33-9. doi: 10.1016/j.ymgme.2010.05.007. Epub 2010 Jun 9.
Medium chain acyl-CoA dehydrogenase deficiency (MCADD) is the most frequent of the fatty acid oxidation disorders (FAOD), a group caused by defects in the mitochondrial B-oxidation of fatty acids. Fatty acid oxidation is critical in supplying energy during periods when glucose is limited or when energy needs are increased beyond the availability of glucose. In MCADD, this energy shortage can result in acute metabolic episodes or sudden death. The prevention of sudden death from MCADD served as the primary impetus to expand newborn screening. However, we have experienced sudden death in four children with MCADD despite their detection by newborn screening. The purpose of this report is to alert others to the danger of sudden death in MCADD even when it is detected by newborn screening, to identify the clinical symptoms that precede sudden death, and to examine the relationship between the newborn screening result and the risk for sudden death.
We describe these children and their metabolic findings with emphasis on their newborn screening octanoylcarnitine (C8) level, the primary marker for newborn detection of MCADD. We also performed a literature search of cases of sudden death in MCADD in which the clinical status preceding death is described.
The newborn screening C8 levels in our four cases were markedly elevated, ranging from 8.4 to 24.8micromol/L (cut off<0.8micromol/L). Only two of the children were homozygous for the common c.985A>G MCAD mutation; the other two were heterozygous for this mutation. Similarly, among the eight reported cases which included MCAD genotypes, five were homozygous for the c.985A>G mutation, while two were heterozygous and one was homozygous for a splice site mutation. Vomiting 12-24h before sudden death was present in all four of our cases, and the review of reported cases of sudden death in MCADD disclosed vomiting as a frequent symptom.
We suggest that in MCADD (1) a newborn screening C8 level of 6micromol/L or greater represents particular risk of sudden death; (2) that MCAD genotypes other than homozygosity for the c.985A>G mutation are also associated with sudden death; (3) that vomiting is a frequent symptom preceding sudden death; and (4) social support and medical follow-up of these families are crucial in reducing the occurrence of sudden death.
中链酰基辅酶 A 脱氢酶缺乏症（MCADD）是脂肪酸氧化障碍（FAOD）中最常见的一种，FAOD 是由脂肪酸在线粒体β氧化过程中的缺陷引起的。脂肪酸氧化在葡萄糖有限或能量需求超过葡萄糖供应时提供能量至关重要。在 MCADD 中，这种能量短缺可能导致急性代谢发作或突然死亡。预防 MCADD 引起的猝死是扩大新生儿筛查的主要动力。然而，尽管通过新生儿筛查发现了 MCADD，但我们还是在四个孩子中经历了猝死。本报告的目的是提醒其他人注意 MCADD 即使通过新生儿筛查也可能导致猝死的危险，确定先于猝死的临床症状，并检查新生儿筛查结果与猝死风险之间的关系。
我们描述了这些孩子及其代谢发现，重点是他们的新生儿筛查辛酰肉碱（C8）水平，这是 MCADD 新生儿检测的主要标志物。我们还对描述了死亡前临床状况的 MCADD 猝死病例进行了文献检索。
我们四个病例的新生儿筛查 C8 水平明显升高，范围为 8.4 至 24.8μmol/L（截断值<0.8μmol/L）。只有两个孩子是常见的 c.985A>G MCAD 突变的纯合子；另外两个是杂合子。同样，在包括 MCAD 基因型的 8 例报告病例中，有 5 例是 c.985A>G 突变的纯合子，2 例是杂合子，1 例是剪接位点突变的纯合子。我们的四个病例在猝死前 12-24 小时都有呕吐，对 MCADD 猝死报告病例的回顾发现呕吐是常见的症状。
我们建议在 MCADD 中：（1）新生儿筛查 C8 水平达到或超过 6μmol/L 代表猝死的特殊风险；（2）c.985A>G 突变以外的 MCAD 基因型也与猝死有关；（3）呕吐是猝死前常见的症状；（4）这些家庭的社会支持和医疗随访对于降低猝死的发生至关重要。
