Clinical, biochemical and molecular findings of 24 Brazilian patients with glutaric acidemia type 1: 4 novel mutations in the GCDH gene.

Autor: Sitta A; Serviço de Genética Médica, Hospital de Clínicas de Porto Alegre, Ramiro Barcelos, 2350, 90035-003, Porto Alegre, RS, Brazil. asitta@hcpa.edu.br., Guerreiro G; Programa de Pós-Graduação em Ciências Farmacêuticas, Universidade Federal do Rio Grande do Sul, Ipiranga, 2752, 90610-000, Porto Alegre, RS, Brazil., de Moura Coelho D; Serviço de Genética Médica, Hospital de Clínicas de Porto Alegre, Ramiro Barcelos, 2350, 90035-003, Porto Alegre, RS, Brazil., da Rocha VV; Serviço de Genética Médica, Hospital de Clínicas de Porto Alegre, Ramiro Barcelos, 2350, 90035-003, Porto Alegre, RS, Brazil., Dos Reis BG; Serviço de Genética Médica, Hospital de Clínicas de Porto Alegre, Ramiro Barcelos, 2350, 90035-003, Porto Alegre, RS, Brazil., Sousa C; Newborn Screening, Metabolism & Genetics Unit, Human Genetics Department, National Institute of Health Dr Ricardo Jorge, Alexandre Herculano, 321, 4000-055, Porto, Portugal., Vilarinho L; Newborn Screening, Metabolism & Genetics Unit, Human Genetics Department, National Institute of Health Dr Ricardo Jorge, Alexandre Herculano, 321, 4000-055, Porto, Portugal., Wajner M; Serviço de Genética Médica, Hospital de Clínicas de Porto Alegre, Ramiro Barcelos, 2350, 90035-003, Porto Alegre, RS, Brazil.; Departamento de Bioquímica, Instituto de Ciências Básicas da Saúde, Universidade Federal de Rio Grande do Sul, Ramiro Barcelos, 2600, Porto Alegre, RS, 90035-003, Brazil., Vargas CR; Serviço de Genética Médica, Hospital de Clínicas de Porto Alegre, Ramiro Barcelos, 2350, 90035-003, Porto Alegre, RS, Brazil. crvargas@hcpa.edu.br.; Programa de Pós-Graduação em Ciências Farmacêuticas, Universidade Federal do Rio Grande do Sul, Ipiranga, 2752, 90610-000, Porto Alegre, RS, Brazil. crvargas@hcpa.edu.br.; Departamento de Bioquímica, Instituto de Ciências Básicas da Saúde, Universidade Federal de Rio Grande do Sul, Ramiro Barcelos, 2600, Porto Alegre, RS, 90035-003, Brazil. crvargas@hcpa.edu.br.
Jazyk: angličtina
Zdroj: Metabolic brain disease [Metab Brain Dis] 2021 Feb; Vol. 36 (2), pp. 205-212. Date of Electronic Publication: 2020 Oct 16.
DOI: 10.1007/s11011-020-00632-0
Abstrakt: Glutaric aciduria type 1 (GA-1) is a rare but treatable inherited disease caused by deficiency of glutaryl-CoA dehydrogenase activity due to GCDH gene mutations. In this study, we report 24 symptomatic GA-1 Brazilian patients, and present their clinical, biochemical, and molecular findings. Patients were diagnosed by high levels of glutaric and/or 3-hydroxyglutaric and glutarylcarnitine. Diagnosis was confirmed by genetic analysis. Most patients had the early-onset severe form of the disease and the main features were neurological deterioration, seizures and dystonia, usually following an episode of metabolic decompensation. Despite the early symptomatology, diagnosis took a long time for most patients. We identified 13 variants in the GCDH gene, four of them were novel: c.91 + 5G > A, c.167T > G, c.257C > T, and c.10A > T. The most common mutation was c.1204C > T (p.R402W). Surprisingly, the second most frequent mutation was the new mutation c.91 + 5G > A (IVS1 ds G-A + 5). Our results allowed a complete characterization of the GA-1 Brazilian patients. Besides, they expand the mutational spectrum of GA-1, with the description of four new mutations. This work reinforces the importance of awareness of GA-1 among doctors in order to allow early diagnosis and treatment in countries like Brazil where the disease has not been included in newborn screening programs.
Databáze: MEDLINE
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