Frequencies of inherited organic acidurias and disorders of mitochondrial fatty acid transport and oxidation in Germany

The lack of epidemiological data on the frequency and/or burden of organic acidurias (OA) and mitochondrial fatty acid transport and oxidation disorders (mtFATOD) is one reason for hesitation to expand newborn screening (NBS) by tandem mass spectrometry (MS-MS). From 1999 to 2000, the frequency of ten potentially treatable OA and mtFATOD was assessed by active nation-wide surveillance on cases presenting with clinical symptoms using the German Paediatric Surveillance Unit (ESPED) system. Case ascertainment was complemented by a second independent source: 3-monthly inquiries in the metabolic laboratories performing secondary selected screening for OA and mtFATOD. Frequency estimates for clinically symptomatic cases older than 7 days in a birth cohort of 844,575 conventionally screened children was compared to the frequency found in a cohort of 382,247 screened by MS-MS in Bavaria and Baden-Württemberg. The overall frequency of the ten conditions considered was 1:8,000 (95% CI 1:11,000–1:6,000) by MS-MS as compared to 1:23,000 (95% CI 1:36,000–1:17,000) in symptomatic cases presenting mainly with metabolic crisis. The contributions of medium-chain acyl-CoA dehydrogenase deficiency (MCADD), other mtFATOD and OA were 29, 4 and 13 among the 46 cases identified by MS-MS, and 19, 1 and 13 among the 33 clinically symptomatic cases, respectively. Acute metabolic crisis, with a lethal outcome in four patients, was reported for 22/33 clinically symptomatic cases. No clinically symptomatic cases were reported from cohorts with screened by MS-MS. Conclusion: ten potentially treatable organic acidurias and mitochondrial fatty acid transport and oxidations disorders were more common than phenylketonuria with organic acidurias accounting for 28% of the cases detected by newborn screening and 39% of the cases identified on high risk screening. These conditions were related to considerable morbidity and mortality. Considerations for their inclusion in expanded newborn screening programmes might be warranted.Abbreviations ESPED Erhebungseinheit für seltene pädiatrische Erkrankungen in Deutschland (German Paediatric Surveillance Unit) - MCADD medium-chain acyl-CoA dehydrogenase deficiency - MS-MS tandem mass spectrometry - mtFATOD mitochondrial fatty acid transport and oxidation disorders - NBS newborn screening - OA organic acidurias