RESUMEN
Glutaric aciduria type 1 (GA1, deficiency of glutaryl CoA dehydrogenase, glutaric acidemia type 1) (ICD-10 code: E72.3; MIM 231670) is an autosomal recessive disease caused by mutations in the gene encoding the enzyme glutaryl CoA dehydrogenase (GCDH). Herein, we present the biochemical and molecular genetic characteristics of 51 patients diagnosed with GA1 from 49 unrelated families in Russia. We identified a total of 21 variants, 9 of which were novel: c.127 + 1G > T, Ñ.471_473delCGA, c.161 T > C (p.Leu54Pro), c.531C > A (Ñ.Phe177Leu), c.647C > T (p.Ser216Leu), c.705G > A (Ñ.Gly235Asp), c.898 G > A (Ñ.Gly300Ser), c.1205G > C (Ñ.Arg402Pro), c.1178G > A (Ñ.Gly393Glu). The most commonly detected missense variants were c.1204C > T (p.Arg402Trp) and Ñ.1262C > T (Ñ.Ala421Val), which were identified in 56.38% and 11.7% of mutated alleles. A heterozygous microdeletion of the short arm (p) of chromosome 19 from position 12,994,984-13,003,217 (8233 b.p.) and from position 12,991,506-13,003,217 (11,711 b.p.) were detected in two patients. Genes located in the area of imbalance were KLF1, DNASE2, and GCDH. Patients presented typical GA1 biochemical changes in the biological fluids, except one patient with the homozygous mutation p.Val400Met. No correlation was found between the GCDH genotype and glutaric acid (GA) concentration in the cohort of our patients.