摘要：Biallelic mutations of the GCDH gene result in Glutaric Aciduria type 1 (GA1; OMIM # 231670 ), an uncommon autosomal recessive inborn error caused by the deficiency of glutaryl-CoA dehydrogenase (CCDH), a mitochondrial matrix protein involved in the degradation of l -lysine, L-hydroxylysine, and L-tryptophan. The enzymatic deficiency leads to the accumulation of neurotoxins causing macrocephaly at birth, hypotonia and dystonia due to bilateral striatal injury, that evolves with aging, if untreated, to fixed dystonia and akinetic-rigid parkinsonism. In this article, we describe the results of molecular studies of 5 unrelated patients with GA1 in Southern Mexico. Mutational analysis identified 2 novel likely pathogenic GCDH variants (p.Leu130Pro and p.Gly391Val), 1 pathogenic variant that is predicted to cause a premature stop codon (p.Leu370*), and 2 previously reported pathogenic variants (p.Arg294Trp and p.Arg294Gln). The recurrence of the p.Leu130Pro variant (60% of mutant alleles) suggested a possible founder mutation effect. Our results expand the mutational spectrum in GA1 patients and support the importance of early diagnosis through newborn screening that promotes early nutritional treatment and prevents metabolic crisis. Take home message Glutaric Aciduria type 1 has a wide mutational spectrum; the p.Leu130Pro variant may be a founder mutation in Southeast Mexico.
