Geographical Variations in MCADD Frequency: Findings from Expanded Newborn Screening in Russia.

Background: Medium-chain acyl-CoA dehydrogenase deficiency (MCADD) is one of Western Europe`s most common mitochondrial fatty acid β-oxidation disorders. The pathogenic variant c.985A>G (p.K329E) accounts for 90% of MCADD cases. This study reports on the first MCADD patients detected via expanded newborn screening in Russia.
Methods: Expanded Newborn Screening for inherited metabolic disorders (IMD) in Russia began in January 2023 by quantification of amino acids and acylcarnitines in dried blood spots using tandem mass spectrometry. Infants with positive screening results were then subject to confirmation by DNA analysis.
Results: Approximately 221 342 infants were screened for IMD since January 2023. Seven infants screened positive for MCADD, and MCADD has been confirmed in three of them. The C8 levels were higher among infants with MCADD (median 9,68 uM/l) compared to those with false-positive results (median 0.425 uM/l). Molecular testing showed that one infant had the c.134A>G mutation in a homozygous state, while the second infant had the c.388-19T>A mutation in a homozygous state. The third infant had c.134A>G/ c.388-19T>A genotype. All three newborns were from the North Caucasus Federal District of the Russian Federation. No infants were identified from the central part of Russia.
Conclusion: Our data show that the frequency of MCADD in Russia (the estimated birth prevalence of MCADD is approximately 1 in 73 780) is not as high as in Western Europe and may vary geographically. The most frequent Western Europe mutation does not seem to be frequent in Russia.