Department of Medical Genetics, MBC-75, King Faisal Specialist Hospital & Research Centre, PO BOX 3345, Riyadh 11211, Saudi Arabia.
J Inherit Metab Dis. 2010 Dec;33 Suppl 3:S263-7. doi: 10.1007/s10545-010-9143-1. Epub 2010 Jun 22.
Medium-chain acyl-CoA dehydrogenase deficiency (MCADD), caused by mutated ACADM gene, is a potentially fatal fatty acid oxidation defect. Detection of MCADD is now part of tandem mass spectrometry (MS-MS)-based newborn screening programs worldwide. To date, more than 67 mutations have been reported to cause MCADD with a single allele, c.985A>G, being the most common in patients of northwestern European descent. In Saudi Arabia, the Newborn Screening Program, officially launched in 2005, screens for 16 disorders including MCADD. Over a period of 3 years, 237,812 newborns were screened; 13 were identified to have MCADD giving an incidence of 1:18,293. Since the introduction of MS-MS to our institution, however, a total of 30 patients were detected to have MCADD. These cases were either newborns, at high-risk family members, or clinically suspected. The C8-carnitine levels (median 3.31, range 0.81-16.33 µM) were clearly diagnostic in all analyzed samples. Sequencing ACADM in 20 DBS revealed two novel mutations: c.362C>T (p.T121I) and c.347G>A (p.C116Y) substitutions, neither of which were detected in 300 chromosomes from controls. Eighteen (90%) patients were homozygous for the T121I mutation and two (10%) were compound heterozygous (T121I/C116Y). Our molecular data lend further support to MS-MS biochemical screening for MCADD and provide evidence for the relatively high incidence of MCADD in the Arab population. The identification of a founder mutation for MCADD has important implications for the preventive screening programs not only in Saudi Arabia but potentially also in other countries in the region.
中链酰基辅酶 A 脱氢酶缺乏症 (MCADD) 是一种潜在致命的脂肪酸氧化缺陷，由 ACADM 基因突变引起。目前，全世界的串联质谱 (MS-MS) 新生儿筛查项目都将 MCADD 检测纳入其中。迄今为止，已有超过 67 种突变被报道可导致 MCADD，其中单个等位基因 c.985A>G 在北欧血统的患者中最为常见。在沙特阿拉伯，新生儿筛查计划于 2005 年正式启动，筛查包括 MCADD 在内的 16 种疾病。在 3 年的时间里，对 237,812 名新生儿进行了筛查；发现 13 例患有 MCADD，发病率为 1:18,293。然而，自从 MS-MS 引入我们的机构以来，共发现 30 例 MCADD 患者。这些病例要么是新生儿，要么是高危家庭成员，要么是临床疑似病例。所有分析样本的 C8-肉碱水平（中位数 3.31，范围 0.81-16.33 µM）均具有明确的诊断价值。对 20 份 DBS 中的 ACADM 进行测序显示了两种新的突变：c.362C>T (p.T121I) 和 c.347G>A (p.C116Y) 取代，在 300 个对照染色体中均未检测到。18 名（90%）患者为 T121I 突变纯合子，2 名（10%）为复合杂合子（T121I/C116Y）。我们的分子数据进一步支持 MCADD 的 MS-MS 生化筛查，并为阿拉伯人群中 MCADD 的相对高发率提供了证据。MCADD 启动子突变的鉴定不仅对沙特阿拉伯，而且对该地区其他国家的预防性筛查计划都具有重要意义。
