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Medium-chain acyl-CoA dehydrogenase deficiency in Saudi Arabia: incidence, genotype, and preventive implications.
MedLine Citation:
PMID:  20567907     Owner:  NLM     Status:  Publisher    
Abstract/OtherAbstract:
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 microM) 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.
Authors:
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
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Publication Detail:
Type:  JOURNAL ARTICLE     Date:  2010-6-22
Journal Detail:
Title:  Journal of inherited metabolic disease     Volume:  -     ISSN:  1573-2665     ISO Abbreviation:  -     Publication Date:  2010 Jun 
Date Detail:
Created Date:  2010-6-22     Completed Date:  -     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  7910918     Medline TA:  J Inherit Metab Dis     Country:  -    
Other Details:
Languages:  ENG     Pagination:  -     Citation Subset:  -    
Affiliation:
Department of Medical Genetics, MBC-75, King Faisal Specialist Hospital & Research Centre, PO BOX 3345, Riyadh, 11211, Saudi Arabia, zhassnan@kfshrc.edu.sa.
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