Large-scale newborn screening for organic acidemias in Quanzhou, China: a 10-year retrospective observational study

Organic acidemias (OADs) are a group of congenital metabolic disorders whose incidence, disease spectrum, and genetic profiles differ greatly across countries. This study aimed to determine the characteristics of OADs in Quanzhou, China. A total of 693,797 newborns were screened for OADs from 2014 to 2023, and the acylcarnitine and genetic profiles of patients with OADs were analysed. Sixty-nine patients were confirmed to have OADs, with an overall incidence of 1/10,055 newborns. Seven types of OADs were identified, of which 18 were 2-methylbutyryl-CoA dehydrogenase deficiency (MBAD), 18 were 3-methylcrotonyl-CoA carboxylase deficiency (3-MCCD), 13 were glutaric acidemia type 1 (GA-1), nine were isobutyryl-CoA dehydrogenase deficiency (IBDD), five were isovaleric acidemia (IVA), four were methylmalonic acidemia (MMA), and two were propionic academia (PA). All but one of the patients with MBAD had elevated isovalerylcarnitine levels and corresponding ratios during screening. All patients with GA-1 had elevated glutarylcarnitine levels and corresponding ratios during screening, except for one with a low free carnitine level. The remaining patients presented with elevated acylcarnitine levels during screening and recall. Several variant hotspots were identified in the ACADSB, MCCC1, MCCC2, GCDH, ACAD8, and IVD. The overall incidence of OADs in the study population was 1/10,055 newborns, with MBAD, 3-MCCD, and GA-1 being the three most common. The acylcarnitine profiles and genetic features of most OADs have been elucidated. Our findings provide useful information for newborn screening, genetic diagnosis, and the prevention of OADs.