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.

1 型戊二酸尿症 (GA-1) 是一种罕见但可治疗的遗传性疾病，由 GCDH 基因突变导致戊二酰辅酶 A 脱氢酶活性缺乏引起。在这项研究中，我们报告了 24 名有症状的 GA-1 巴西患者，并介绍了他们的临床、生化和分子研究结果。患者被诊断为高水平的戊二酸和/或 3-羟基戊二酸和戊二酰肉碱。通过基因分析证实了诊断。大多数患者患有早发性严重疾病，主要特征是神经功能恶化、癫痫发作和肌张力障碍，通常发生在代谢失代偿期之后。尽管有早期症状，但大多数患者的诊断需要很长时间。我们在 GCDH 基因中发现了 13 个变异，其中四个是新的：c.91 + 5G > A、c.167T > G、c.257C > T 和 c.10A > T。最常见的突变是 c.1204C > T (p.R402W)。令人惊讶的是，第二个最常见的突变是新突变 c.91 + 5G > A (IVS1 ds GA + 5)。我们的结果允许对 GA-1 巴西患者进行完整的表征。此外，他们扩展了 GA-1 的突变谱，描述了四个新突变。这项工作加强了医生对 GA-1 认识的重要性，以便在巴西等尚未将该疾病纳入新生儿筛查计划的国家进行早期诊断和治疗。与四个新突变的描述。这项工作加强了医生对 GA-1 认识的重要性，以便在巴西等尚未将该疾病纳入新生儿筛查计划的国家进行早期诊断和治疗。与四个新突变的描述。这项工作加强了医生对 GA-1 认识的重要性，以便在巴西等尚未将该疾病纳入新生儿筛查计划的国家进行早期诊断和治疗。