Medium-chain acyl-CoA dehydrogenase deficiency in Saudi Arabia: incidence, genotype, and preventive implications.
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.
Al-Hassnan
Zuhair N
ZN
Department of Medical Genetics, MBC-75, King Faisal Specialist Hospital & Research Centre, PO BOX 3345, Riyadh 11211, Saudi Arabia. zhassnan@kfshrc.edu.sa
Imtiaz
Faiqa
F
Al-Amoudi
Mohamed
M
Rahbeeni
Zuhair
Z
Al-Sayed
Moeen
M
Al-Owain
Mohammed
M
Al-Zaidan
Hamad
H
Al-Odaib
Ali
A
Rashed
Mohamed S
MS
D042964:Acyl-CoA Dehydrogenase / Q000097:blood / Q000172:deficiency / Q000235:genetics*; D015415:Biomarkers / Q000097:blood; D002331:Carnitine / Q000097:blood; D004252:DNA Mutational Analysis; D059788:Dried Blood Spot Testing; D018703:Founder Effect; D005787:Gene Frequency; D020022:Genetic Predisposition to Disease; D005820:Genetic Testing / Q000379:methods; D006801:Humans; D015994:Incidence; D007231:Infant, Newborn; D008052:Lipid Metabolism, Inborn Errors / Q000097:blood / Q000175:diagnosis / Q000201:enzymology / Q000453:epidemiology / Q000235:genetics / Q000517:prevention & control; D009154:Mutation; D015997:Neonatal Screening / Q000379:methods; D010641:Phenotype; D011237:Predictive Value of Tests; D012529:Saudi Arabia / Q000453:epidemiology; D053719:Tandem Mass Spectrometry
D015415:Biomarkers; D042964:Acyl-CoA Dehydrogenase; D002331:Carnitine