Glutaric aciduria type 1: Insights into diagnosis and neurogenetic outcomes.

Unlabelled: 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.

Conclusion: 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.

What Is Known: • 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.

What Is New: • 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.