Yoldas Celik Merve, Canda Ebru, Yazici Havva, Erdem Fehime, Yuksel Yanbolu Ayse, Atik Altınok Yasemin, Eraslan Cenk, Aykut Ayca, Durmaz Asude, Habif Sara, Kalkan Ucar Sema, Coker Mahmut
Department of Pediatric Metabolism and Nutrition, Medical Faculty, Ege University, Izmir, 35040, Turkey.
Department of Radiology, Medical Faculty, Ege University, Izmir, 35040, Turkey.
Eur J Pediatr. 2024 Dec 10;184(1):72. doi: 10.1007/s00431-024-05907-7.
Glutaric aciduria type 1 (GA1) is a rare metabolic disorder characterized by a deficiency in the enzyme glutaryl-CoA dehydrogenase. This study aims to present the clinical, biochemical, genetic, and neuroimaging findings of GA1 patients, emphasizing the importance of early detection and the potential benefits of incorporating GA1 into NBS programs. The demographic, clinical, and laboratory findings of GA1 patients were reviewed retrospectively. This study presents the clinical, biochemical, genetic, and neuroimaging findings of 15 patients (six males, nine females) from 13 families diagnosed with GA1. The median age at diagnosis was 20 months, and the median follow-up period was 72 months. Developmental delay was observed in 66.7% of patients, with 46.7% experiencing seizures and 33.3% suffering from encephalopathic crises. Biochemical analyses showed elevated levels of glutaric acid and 3-hydroxyglutaric acid in 93.3% and 80% of patients, respectively. Genetic testing identified the p.Arg402Trp variant in 53.3% of patients. Neurological evaluations revealed delays in motor and speech development, with 66.7% of patients never achieving the ability to walk. Cranial MRI indicated white matter changes in all patients and basal ganglia involvement in 93.3%. Despite significant biochemical improvements with treatment in glutaric acid levels and head circumference over time, neurological deficits remain unchanged. Growth parameters such as body weight showed significant decreases due to poor neurological outcomes.
The study underscores the importance of early diagnosis and intervention to mitigate severe neurological outcomes. Our findings highlight the need for incorporating GA1 into newborn screening programs to ensure timely diagnosis and treatment.
• Glutaric aciduria type 1 (GA1) is a rare metabolic disorder caused by a deficiency of glutaryl-CoA dehydrogenase. If untreated, it often leads to severe neurological complications. Early diagnosis and treatment are crucial for improving clinical outcomes in GA1 patients.
• This study presents comprehensive data from a cohort of 15 Glutaric aciduria type 1 (GA1) patients, detailing their biochemical, genetic, clinical, and neuroimaging findings. Drawing attention to the severe neurological findings in late-diagnosed patients underscores the critical importance of including GA1 in newborn screening programs to enhance early diagnosis and prevent severe outcomes.
1型戊二酸血症（GA1）是一种罕见的代谢紊乱疾病，其特征是戊二酰辅酶A脱氢酶缺乏。本研究旨在介绍GA1患者的临床、生化、遗传和神经影像学检查结果，强调早期检测的重要性以及将GA1纳入新生儿疾病筛查项目的潜在益处。对GA1患者的人口统计学、临床和实验室检查结果进行了回顾性分析。本研究介绍了13个家庭中15例（6例男性，9例女性）被诊断为GA1患者的临床、生化、遗传和神经影像学检查结果。诊断时的中位年龄为20个月，中位随访期为72个月。66.7%的患者出现发育迟缓，46.7%的患者出现癫痫发作，33.3%的患者发生脑病危象。生化分析显示，93.3%的患者戊二酸水平升高，80%的患者3-羟基戊二酸水平升高。基因检测发现53.3%的患者存在p.Arg402Trp变异。神经学评估显示运动和语言发育延迟，66.7%的患者从未获得行走能力。头颅磁共振成像显示所有患者均有白质改变，93.3%的患者有基底节受累。尽管随着时间的推移，治疗使戊二酸水平和头围有了显著的生化改善，但神经功能缺损仍未改变。由于神经学预后不良，体重等生长参数显著下降。
该研究强调了早期诊断和干预以减轻严重神经学后果的重要性。我们的研究结果凸显了将GA1纳入新生儿筛查项目以确保及时诊断和治疗的必要性。
• 1型戊二酸血症（GA1）是一种由戊二酰辅酶A脱氢酶缺乏引起的罕见代谢紊乱疾病。如果不进行治疗，它通常会导致严重的神经并发症。早期诊断和治疗对于改善GA1患者的临床预后至关重要。
• 本研究展示了一组15例1型戊二酸血症（GA1）患者的全面数据，详细介绍了他们的生化、遗传、临床和神经影像学检查结果。关注晚期诊断患者的严重神经学检查结果凸显了将GA1纳入新生儿筛查项目以加强早期诊断和预防严重后果的至关重要性。
