Biochemical and molecular features of chinese patients with glutaric acidemia type 1 from Fujian Province, southeastern China

Abstract

Background Glutaric acidemia type 1 (GA1) is a rare autosomal recessive inherited metabolic disorder caused by variants in the gene encoding the enzyme glutaryl-CoA dehydrogenase (GCDH). The estimated prevalence of GA1 and the mutational spectrum of the GCDH gene vary widely according to race and region. The aim of this study was to assess the acylcarnitine profiles and genetic characteristics of patients with GA1 in Fujian Province, southeastern China. Results From January 2014 to December 2022, a total of 1,151,069 newborns (631,016 males and 520,053 females) were screened using MS/MS in six newborn screening (NBS) centers in Fujian Province and recruited for this study. Through NBS, 18 newborns (13 females and 5 males) were diagnosed with GA1. Thus, the estimated incidence of GA1 was 1 in 63,948 newborns in Fujian province. In addition, 17 patients with GA1 were recruited after clinical diagnosis. All but one patient with GA1 had a remarkable increase in glutarylcarnitine (C5DC) concentrations. The results of urinary organic acid analyses in 33 patients showed that the concentration of glutaric acid (GA) increased in all patients. The levels of C5DC and GA in patients identified via NBS were higher than those in patients identified via clinical diagnosis (P < 0.05). A total of 71 variants of 70 alleles were detected in patients with GA1, with 19 different pathogenic variants identified. The three most prevalent variants represented 73.23% of the total and were c.1244-2 A > C, p.(?) (63.38%), c.1261G > A, p.Ala421Thr (5.63%), and c.406G > T, p.Gly136Cys (4.22%). The most abundant genotype observed was c.[1244-2 A > C]; [1244-2 A > C] (18/35, 52.43%) and its phenotype corresponded to high excretors (HE, GA > 100 mmol/mol Cr). Conclusions In conclusion, we investigated the biochemical and molecular features of 35 unrelated patients with GA1. C5DC concentrations in dried blood spots and urinary GA are effective indicators for a GA1 diagnosis. Our study also identified a GCDH variant spectrum in patients with GA1 from Fujian Province, southeastern China. Correlation analysis between genotypes and phenotypes provides preliminary and valuable information for genetic counseling and management.

Screening and the analysis of genotypic and phenotypic characterization of glucose-6-phosphate dehydrogenase (G6PD) deficiency in Fujian province, China

“…The workflow of NBS was based on a previously described procedure ( Qiu et al, 2023 ; Zhou et al, 2023 ). Briefly, After drying at room temperature, the dried blood spot samples were transported to the NBS center the next day using a cold-chain transportation system.…”