Abstract
BACKGROUND: Glutaric acidemia type 1 (GA-1) is a rare autosomal recessive metabolic disorder resulting from a deficiency in glutaryl-CoA dehydrogenase (GCDH). Current evidence indicates that GA-1 remains under-recognized by clinicians, a factor that may contribute to delayed diagnosis. The aim of this study was to retrospectively analyze the clinical manifestations and imaging characteristics of GA-1. METHODS: This study enrolled patients diagnosed with GA-1 at the Guangzhou Women and Children's Medical Center between April 2014 and April 2024. Clinical data related to GA-1 were retrieved through the electronic medical record system, and magnetic resonance imaging (MRI) scans were collected for all patients. Cranial MRI images were independently evaluated by two radiologists (with 10 and 6 years of experience in pediatric neuroimaging diagnosis, respectively) using a blinded approach. Blood acylcarnitine levels were analyzed using tandem mass spectrometry, urinary organic acid concentrations were quantified via gas chromatography-mass spectrometry, and GCDH gene analysis was performed in a subset of patients. RESULTS: This study enrolled 24 GA-1 children (8 males, 16 females) from Guangdong Province, China. Diagnosis was confirmed by elevated glutaric acid (GA), 3-hydroxyglutaric acid (3-HGA), and glutarylcarnitine (C5DC) levels, with increased C5DC/octanoylcarnitine (C8) and C5DC/propionylcarnitine (C3) ratios. Genetic analysis identified 12 GCDH mutations in 11 patients, including 5 novel variants (c.395G>A, c.271+1G>A, c.1156C>G, c.146_149delACTG, and c.1011A>G). Neuroimaging revealed abnormal brain MRI findings in all patients (100%), predominantly featuring frontotemporal extracerebral space widening (75.0%, 18/24) and symmetric basal ganglia hyperintensity (83.3%, 20/24). These findings align with the established GA-1 phenotypes. CONCLUSIONS: This study underscores the need for heightened awareness of GA-1 among clinicians and radiologists, characterizes its MRI signature, and expands the GCDH mutation spectrum with five novel variants, thereby offering valuable guidance for imaging-based diagnosis and genetic counselling.