Glutaric Acidemia Type 1

Glutaric acidemia type 1 (GA1) is an autosomal recessive metabolic disorder caused by a deficiency of glutaryl-CoA dehydrogenase (GCDH), an enzyme involved in the catabolism of lysine, hydroxylysine, and tryptophan. This deficiency leads to the accumulation of glutaric acid and other metabolites in body fluids and tissues, particularly the brain. Clinically, GA1 typically presents in infancy or early childhood with acute encephalopathic crises, often triggered by intercurrent infections or other stressors. These crises can result in irreversible damage to the basal ganglia, leading to dystonia, choreoathetosis, and developmental delay. Macrocephaly is a common early finding. Diagnosis is based on newborn screening, urine organic acid analysis, plasma acylcarnitine analysis, and genetic testing. MRI of the brain may reveal characteristic changes in the basal ganglia. Treatment focuses on dietary restriction of lysine, supplementation with L-carnitine, and aggressive management of metabolic crises. Early diagnosis and treatment are crucial to prevent or minimize neurological sequelae.