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Medium‐chain acyl‐CoA dehydrogenase deficiency in Saudi Arabia: incidence, genotype, and preventive implications
Author(s) -
AlHassnan Zuhair N.,
Imtiaz Faiqa,
AlAmoudi Mohamed,
Rahbeeni Zuhair,
AlSayed Moeen,
AlOwain Mohammed,
AlZaidan Hamad,
AlOdaib Ali,
Rashed Mohamed S.
Publication year - 2010
Publication title -
journal of inherited metabolic disease
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.462
H-Index - 102
eISSN - 1573-2665
pISSN - 0141-8955
DOI - 10.1007/s10545-010-9143-1
Subject(s) - genotype , incidence (geometry) , medicine , enzyme , genetics , biology , biochemistry , gene , physics , optics
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.