Glutaric Aciduria Type I (GA-1) is an autosomal recessive neurometabolic disorder characterised by the accumulation of toxic metabolites due to Glutaryl-CoA Dehydrogenase (GCDH) deficiency, leading to striatal damage and neurodegeneration. GA-1 often presents in early infancy with acute neurological crises, including seizures and encephalopathy, with macrocephaly as a potential early sign. We present a case series of five infants suspected of GA-1, who were evaluated clinically, radiologically, and biochemically for seizures, macrocephaly, or encephalopathy. Investigations included Tandem Mass Spectrometry (TMS) and Gas Chromatography-Mass Spectrometry (GCMS). Magnetic Resonance Imaging (MRI) of the brain with contrast and Electroencephalography (EEG) were also performed. Out of the five cases, two (Case 1 and Case 2) were positively confirmed with GA-1, demonstrating classical neuroimaging findings such as the “bat wing” appearance due to widened Sylvian fissures, frontotemporal atrophy, and characteristic basal ganglia hyperintensities. These cases also showed elevated glutarylcarnitine and 3-hydroxyhexanoylcarnitine on TMS, along with high levels of urinary glutaric acid, 3-hydroxyglutaric acid, and glutaconic acid on GCMS. The remaining three cases (Case 3, Case 4, and Case 5) presented with compatible clinical scenarios (e.g., seizures), but their neuroimaging and biochemical findings were either subtle, non-specific, or equivocal for GA-1, necessitating ongoing follow-up and longitudinal assessment. EEG in symptomatic infants showed intermittent centro-parietal epileptiform discharges. GA-1 should be considered in infants presenting with seizures or encephalopathy, particularly when MRI demonstrates basal ganglia involvement and widened opercula. Neuroimaging often provides the earliest and most reliable diagnostic clues, serving as critical indicators for subsequent comprehensive biochemical investigations. Prompt diagnosis through this integrated approach is essential to initiate timely dietary and pharmacologic interventions and prevent irreversible neurological injury.
Doshi et al. (Fri,) studied this question.