Age at symptom onset predicts severity of motor impairment and clinical outcome of glutaric acidemia type 1

Objectives: In patients with glutaric acidemia type 1 (GAI), biochemical and molecular markers fail to predict the course of individual patients; therefore we sought to identify nonbiochemical variables that correlate with severity of motor deficits or overall clinical outcome. Study design: Archival data was collected from 42 published articles describing 115 patients with GAI. A forward, stepwise, multiple regression analysis was used to find predictors for outcome. Results: Analyses show that in patients who did not have a precipitating illness before the first appearance of motor symptoms, the age at onset was significantly associated with the severity of motor impairments and overall clinical outcome. In patients who had a precipitating illness, the age at onset did not predict the outcome. In both groups of patients, basal ganglia degeneration, enlargement of spaces containing cerebrospinal fluid, and white matter abnormalities were indicative of a poorer prognosis. Treatment given after the appearance of symptoms was not associated with a better clinical outcome or fewer motor deficits. Conclusion: Because the age at symptom onset can significantly predict the severity of motor deficits and the overall outcome, it is important to identify patients with GAI as early as possible. Several studies suggest that presymptomatic treatment may prevent or postpone the onset of symptoms.