Erschienen in:
01.12.2010 | Research Report
Medium-chain acyl-CoA dehydrogenase deficiency in Saudi Arabia: incidence, genotype, and preventive implications
verfasst von:
Zuhair N. Al-Hassnan, Faiqa Imtiaz, Mohamed Al-Amoudi, Zuhair Rahbeeni, Moeen Al-Sayed, Mohammed Al-Owain, Hamad Al-Zaidan, Ali Al-Odaib, Mohamed S. Rashed
Erschienen in:
Journal of Inherited Metabolic Disease
|
Sonderheft 3/2010
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Abstract
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.