JIMD Reports, Volume 40

Bimal Patel, Surekha Pendyal, Priya S. Kishnani, Marie McDonald, Lauren Bailey, Patel, Bimal, Pendyal, Surekha, Kishnani, Priya S., McDonald, Marie, Bailey, Lauren

Glutaric acidemia type 1 (GA-1, OMIM no. 231670) is an autosomal recessive disorder caused by the deficiency of glutaryl-CoA dehydrogenase (GCDH). The subsequent accumulation of the amino acids lysine, hydroxylysine, and tryptophan and their breakdown intermediates can be neurotoxic and particularly cause injury to the basal ganglia.Roughly 1 of 100,000 infants is affected with GA-1, and a common feature at birth is macrocephaly. Stress, such as in febrile illnesses, can precipitate encephalopathic crises in children generally less than 2 years with variable recovery. Many infants develop dystonia with complex movement disorders and subtle cognitive and fine motor deficits. Common neuroradiologic findings include hypoplasia of temporal and frontal lobes, striatal lesions, white matter changes, and subdural effusions.There are three previous reports of subependymal nodules found on neuroimaging in GA-1 patients who were diagnosed as adults and untreated for GA-1. We present a unique case of an adult female who was diagnosed at age 2 months and managed prior to any metabolic decompensation. Her initial diagnosis was made based on biochemical and enzymatic analysis, and then later confirmed with genetic sequencing. She started experiencing frequent headaches at age 12 years. Neuroimaging in adulthood revealed common features seen in GA-1 in addition to the finding of subependymal nodules.This case may provide some insight into the natural progression of the disease despite early treatment. Though subependymal nodules are typically seen in tuberous sclerosis, the significance of these lesions in GA-1 is not well understood. Disease courses of more early diagnosed and treated patients with GA-1 need to be documented.