The difference between observed and expected prevalence of MCAD deficiency in The Netherlands: a genetic epidemiological study.
Medium chain acyl coenzyme A dehydrogenase (MCAD) deficiency is assumed to be the most common inherited disorder of mitochondrial fatty acid oxidation. Few reports mention the difference between the expected and observed prevalence of MCAD deficiency on the basis of the carrier frequency in the population. We performed a population-wide retrospective analysis of all known MCAD-deficient patients in The Netherlands. In this study, the observed prevalence of MCAD deficiency in The Netherlands was 1/27 400 (95% confidence interval (CI) 1/23 000-1/33 900), significantly different from the expected prevalence of 1/12 100 (95% CI 1/8450-1/18 500). The observed prevalence of MCAD deficiency showed a remarkable north-south trend within the country. From the patients in this cohort, it can be observed that underdiagnosis contributes to a larger extent to the difference between the expected and observed prevalences of MCAD deficiency in our country, than reduced penetrance. We determined estimates of the segregation proportion in a cohort of 73 families under the assumption of complete ascertainment (p(LM) = 0.41, 95% CI 0.31-0.51) and single ascertainment (p(D) = 0.28, 95% CI 0.19-0.37). With the expectation-maximization algorithm, a third estimate was obtained (p(EM) = 0.28, 95% CI 0.20-0.37). The agreement between the latter two estimates supports incomplete selection and the segregation proportions were in agreement with normal mendelian autosomal recessive inheritance.
Derks
Terry G J
TG
Department of Metabolic Diseases, Beatrix Children's Hospital, University Medical Centre, Groningen, The Netherlands. t.g.j.derks@bkk.umcg.nl
Duran
Marinus
M
Waterham
Hans R
HR
Reijngoud
Dirk-Jan
DJ
Ten Kate
Leo P
LP
Smit
G Peter A
GP
D042964:Acyl-CoA Dehydrogenase / Q000172:deficiency* / Q000235:genetics; D000465:Algorithms; D015331:Cohort Studies; D016021:Epidemiologic Studies; D005787:Gene Frequency; D005820:Genetic Testing; D006801:Humans; D007231:Infant, Newborn; D008052:Lipid Metabolism, Inborn Errors / Q000453:epidemiology / Q000235:genetics; D009426:Netherlands / Q000453:epidemiology; D015995:Prevalence; D012189:Retrospective Studies
D042964:Acyl-CoA Dehydrogenase