Introduction

Glutaric aciduria type 1 (GA1) is a rare and inherited autosomal-recessive metabolic disorder that occurs in the deficiency of glutaryl-co-enzyme A dehydrogenase (GCDH) enzyme encoded by GCDH gene. In this study, we aim to retrospectively investigate the clinical, biochemical, and neuroradiological parameters and examine the spectrum of GCDH gene variants in Turkish patients with glutaric aciduria type 1.

Methods

This is a descriptive cross-sectional study. The study was conducted in fifty-three patients from 39 unrelated Turkish families who were diagnosed with GA1 based on their clinical presentation, neuroimaging, and biochemical measurements, at the department of pediatric metabolism of a university hospital between June 1998 and August 2019. Pathogenic variants screening of GCDH gene was performed by direct DNA sequence analysis in forty-six patients with GA1. Pathogenicity of the novel variants was predicted via computational programs.

Results

A total of 53 patients were diagnosed with GA1. Of those, 32 (60.3%) had encephalopathic crisis and 33 (62.3%) had macrocephaly.

Twenty different pathogenic variants were detected, 7 of which are novel (p.Glu57Lys, p.Ser145Profs*79, p.Ser246Glyfs*96 p.Ala293Val, p.His348Gln, p.His417Tyr, p.Asp418Val). The p.Arg402Trp, p.Pro248Leu and p.Leu340Phe variants were the most common in Turkish patients, with a frequency of 21.2%, 18.2% and 12.1% respectively.

Conclusion

This study is the first comprehensive research from Turkey that provides information about disease-causing variants in the GCDH gene. The identification of common variants and hot spot regions of the GCDH gene is important for genetic counselling and the prenatal diagnosis of Turkish patients with GA1.

中文翻译：

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戊二酸尿症1型：53例患者的遗传和表型谱。

介绍

1型戊二酸尿症（GA1）是一种罕见的遗传性常染色体隐性代谢疾病，发生在GCDH基因编码的戊二酰辅酶A脱氢酶（GCDH）缺乏时。在这项研究中，我们旨在回顾性研究土耳其1型戊二酸尿症患者的临床，生化和神经放射学参数，并检查GCDH基因变异的光谱。

方法

这是描述性的横断面研究。这项研究是在1998年6月至2019年8月之间，在一家大学医院的儿科代谢科中对来自39个无关土耳其家庭的53例患者进行了诊断，这些患者根据其临床表现，神经成像和生化指标被诊断为GA1。通过直接DNA序列分析对46例GA1患者进行GCDH基因筛选。新变体的致病性是通过计算程序预测的。

结果

共有53例患者被诊断患有GA1。其中32例（60.3％）患有脑病，33例（62.3％）患有大头畸形。

检测到20种不同的致病变体，其中7种是新的（p.Glu57Lys，p.Ser145Profs * 79，p.Ser246Glyfs * 96 p.Ala293Val，p.His348Gln，p.His417Tyr，p.Asp418Val）。p.Arg402Trp，p.Pro248Leu和p.Leu340Phe变体在土耳其患者中最常见，频率分别为21.2％，18.2％和12.1％。

结论

这项研究是土耳其进行的第一项综合研究，提供了有关GCDH基因致病变异的信息。鉴定GCDH基因的常见变异和热点区域对于遗传咨询和土耳其GA1患者的产前诊断非常重要。