Ethnicity of children with homozygous c.985A>G medium-chain acyl-CoA dehydrogenase deficiency: findings from screening approximately 1.1 million newborn infants

Abstract

Objectives It has been suggested that homozygous c.985A>G medium-chain acyl-CoA dehydrogenase deficiency (MCADD) is a disease of White ethnic origin but little is known regarding its ethnic distribution. We estimated ethnic-specific homozygous c.985A>G MCADD birth prevalence from a large-scale UK newborn screening study. Methods Homozygous c.985A>G MCADD cases were ascertained in six English newborn screening centres between 1 March 2004 and 28 February 2007 by screening approximately 1.1 million newborns using tandem mass spectrometry analysis of underivatised blood spot samples to quantitate octanoylcarnitine (C8). Follow-up biochemistry and mutation analyses for cases (mean triplicate C8 value ≥0.5 µmol/L) were reviewed to confirm diagnosis. Ethnicity was ascertained from clinician report and denominators from 2001 UK Census estimates of ethnic group of children less than one year. Results Sixty-four infants were c.985A>G MCADD homozygotes (overall prevalence 5.8 per 100,000 live births; 95% CI 4.4–7.2). Sixty (93%) were White, two (3%) were mixed/other and two were of unknown ethnic origin. No Asian or Black homozygotes were identified. Proportions of White, mixed/other, Asian and Black births in screening regions were estimated, yielding homozygous c.985A>G MCADD birth prevalence of 6.9 per 100,000 (95% CI 5.2–8.8) in White, and 95% CI estimates of 0–2.7 per 100,000 in Asian and 0–5.8 in Black populations. The c.985A>G carrier frequency in the White group was estimated at one in 65 (95% CI 1/74, 1/61) under Hardy–Weinberg conditions. Conclusion c.985A>G homozygous MCADD is not found in Black and Asian ethnic groups that have been screened at birth in England. This is consistent with the earlier published observations suggesting that MCADD due to the c.985A>G mutation is a disease of White ethnic origin.

Birth Prevalence of Fatty Acid β-Oxidation Disorders in Iberia

“…The same is observed in Spain but to a less extent. This bias in the ethnical distribution of MCADD patients represents a significant difference in MCADD epidemiology in Iberia, namely Portugal, in comparison with other European countries where patients are almost exclusively of non-Gypsy origin (Khalid et al 2008). This particular characteristic of Portuguese Gypsy community is the main justification for the observed birth prevalence of FAOD in Portugal, the highest among countries with available comparable data.…”

Relationship of Octanoylcarnitine Concentrations to Age at Sampling in Unaffected Newborns Screened for Medium-Chain Acyl-CoA Dehydrogenase Deficiency

“…We recently reported the heterozygote frequency of c.985AϾG to be 1/65 in the UK newborn population (19 ). From this, we estimate that in this study we would expect 2722 c.985AϾG heterozygotes among the 179 916 unaffected newborns screened in England over the study period (comprising 179 729 unaffected and 187 previously excluded infants).…”

Newborn screening for medium chain acyl CoA dehydrogenase deficiency

“…Some of the mutations identified in MCADD cases detected by newborn screening have not been described in children who have presented clinically, raising questions over their clinical relevance 27 30. The common mutation is less prevalent outside populations of European descent31 and many other mutations have been identified 22. Thus extended mutation screening is necessary, particularly for those who are not of European descent.…”