Neurological manifestations in glutaric acidemia type 1 and the impact of expanded neonatal screening in Brazil

Abstract

Glutaric acidemia type 1 (GA1) is an inborn error of metabolism caused by the deficiency of the enzyme glutaryl-CoA dehydrogenase, with consequent accumulation of the aminoacids lysine, hydroxylsine and tryptophan. About 1 in every 100,000 individuals are affected by the disease. Neurological manifestations are variable and include acute and chronic encephalopathic crises, dystonia, motor and cognitive deficits, as well as neuroimaging findings such as brain hypoplasia, striatal, white matter and subdural effusions. Early diagnosis is crucial for specific therapy, which includes a diet with restricted amino acids and carnitine replacement. The present work describes the variability of neurological manifestations in four patients with glutaric acidemia type 1, diagnosed in different age groups, through mass spectrometry, technology of the expanded neonatal screening available in the Ministry of Health program in Federal District, Brazil. Complications of GA1 were more severe in cases with later diagnosis, which justifies the use of the enlarged neonatal screening as an important resource in the early diagnosis and treatment of inborn errors of metabolism.