Biochemical and molecular features of Chinese patients with glutaric acidemia type 1 detected through newborn screening

Abstract Background Glutaric acidemia type 1 (GA1) is a treatable disorder affecting cerebral organic acid metabolism caused by defective glutaryl-CoA dehydrogenase ( GCDH ) gene. GA1 diagnosis reports following newborn screening (NBS) are scarce in the Chinese population. This study aimed to assess acylcarnitine profiles and genetic characteristics of patients with identified through NBS. Results From January 2014 September 2020, 517,484 newborns were screened tandem mass spectrometry, 102 elevated glutarylcarnitine (C5DC) levels called back. Thirteen diagnosed GA1, including 11 neonatal two maternal patients. The incidence Quanzhou region was estimated at 47,044 newborns. initial NBS results showed that all but one had moderate markedly increased C5DC levels. Notably, patient low free carnitine (C0) level suggest primary deficiency (PCD) ultimately as GA1. Nine underwent urinary analyses: eight GA 3HGA levels, reported be within normal range. Ten distinct variants identified. Eight previously reported, newly In silico prediction tools protein modeling analyses suggested potentially pathogenic. most common variant c.1244-2 A>C, which an allelic frequency 54.55% (12/22), followed c.1261G>A (p.Ala421Thr) 9.09% (2/22). Conclusions Neonatal can Maternal also detected using due C0 their infants. Few may have atypical easy miss during NBS; therefore, multigene panel testing should performed indicates spectra heterogeneous this southern cohort.