Clinical Spectrum, Neuroimaging, Dietary Management, and Outcomes in Glutaric Aciduria Type I: A Case Series from a Tertiary Metabolic Centre in India

Background: Glutaric aciduria type I (GA1) is a rare autosomal recessive neurometabolic disorder caused by a deficiency of glutaryl-CoA dehydrogenase, leading to the accumulation of glutaric acid, 3-hydroxyglutaric acid, and glutarylcarnitine. The condition predominantly affects the basal ganglia and cerebral cortex and is associated with acute neuroregression, dystonia, and macrocephaly. Early diagnosis and dietary management significantly improve outcomes, but delays are common in low-resource settings.

Purpose: This study aimed to describe the clinical spectrum, diagnostic challenges, neuroimaging features, treatment strategies, and short-term outcomes of children with Glutaric Aciduria Type I (GA1) managed at a tertiary care metabolic center in Rajasthan, India, thereby highlighting the importance of early recognition and timely dietary intervention in improving prognosis.

Methods: We conducted a retrospective review of children diagnosed with GA1 at a tertiary care metabolic center in Rajasthan, India, between June 2023 to September 2024. Diagnosis was based on clinical features, biochemical analysis using tandem mass spectrometry (TMS) and gas chromatography-mass spectrometry (GC-MS), neuroimaging, and where available, genetic testing. Clinical presentation, neuroimaging findings, treatment, and outcomes were analyzed.

Results: Out of 44 children with suspected inborn errors of metabolism evaluated during the study period, 7 (18.4%) were diagnosed with GA1. The mean age at symptom onset was 7.4 ± 2.3 months, and mean age at diagnosis was 21.5 ± 16.7 months. Macrocephaly was present in 85.7%, and 71.4% had acute encephalopathic crises triggered by infections. All children exhibited dystonia; two also had spastic quadriparesis. Neuroimaging showed frontotemporal atrophy with open opercula in all cases and basal ganglia changes in six. Biochemical testing confirmed elevated glutarylcarnitine (C5DC) in all patients, and urine organic acid analysis revealed elevated glutaric and 3-hydroxyglutaric acid in six. Genetic testing in three children identified GCDH mutations, including c.1204C>T in two. A lysine-restricted diet, carnitine supplementation, and emergency care procedures were used to treat every child. Three children remained severely disabled, two had moderate dystonia, and three had minimal deficits after an average follow-up of 18.2 ± 6.3 months.

Conclusions: In infants with dystonia, developmental delay or regression and macrocephaly, GA1 must be suspected, particularly when combined with distinctive neuroimaging findings. Results can be greatly enhanced by early diagnosis and the start of dietary and supportive therapy. Expanded use of genetic counseling, early dietary intervention, and newborn screening is necessary to lower the long-term morbidity linked to GA1 in settings with limited resources.