首页|Biochemical, molecular, and clinical features of patients with glutaric acidemia type 1 identified through large-scale newborn screening in Zhejiang Province, China
Biochemical, molecular, and clinical features of patients with glutaric acidemia type 1 identified through large-scale newborn screening in Zhejiang Province, China
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NSTL
Elsevier
Background: Glutaric acidemia type 1 (GA1) is a treatable neurometabolic disorder caused by biallelic variants in the glutaryl-CoA dehydrogenase (GCDH) gene. There are few large-scale reports describing newborn screening (NBS) for GA1 in China. We report the NBS results, genotypes, and clinical features of patients diagnosed through NBS.Methods: From January 2009 to August 2021, 4,202,587 newborns were screened by tandem mass spectrometry. Newborns with increased glutarylcarnitine (C5DC) concentrations were recalled for repeated test, and confir-matory examinations were performed if the second test was still positive. The pathogenicity of novel variants was predicted using computational programs.Results: A total of 693 had increased C5DC concentrations, and 19 patients were diagnosed with GA1. Thus, the estimated incidence of GA1 in Zhejiang Province was 1 in 221,053 newborns. All the 19 patients had markedly increased C5DC concentrations and C5DC/octanoylcarnitine (C8) ratios; one had a slightly low free carnitine concentration. Seventeen (17/18, 94.4%) patients had increased GA concentrations, 15 were of high excretor phenotype and 3 were of low excretor phenotype. Twenty-three distinct GCDH variants were detected, of which 2were novel. Novel variants were predicted to be potentially pathogenic by computational programs. c.1244-2A > C was the most common variant, with an allelic frequency of 14.7%, followed by c.914C > T (p.S305L) (8.8%). The most common clinical symptom was movement disorder, followed by seizure, macrocephaly, and failure to thrive. Sylvian fissures widening was the most common MRI finding.Conclusions: Nineteen GA1 patients were diagnosed through the large-scale NBS in Zhejiang Province, with an estimated incidence of 1 in 221,053 newborns. The GCDH mutational spectrum is heterogenous, with the c.1244 -2A > C variant being the most frequent variant in this population. NBS for GA1 should be promoted to achieve timely diagnosis and treatment.
Glutaric acidemia type 1glutaryl-CoA dehydrogenaseNewborn screeningGCDH geneACIDURIA TYPE-IPHENOTYPEGENOTYPE
NSTL
Elsevier
