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


METHODS
Archival data was collected from 42 published articles describing 115 patients with GA1. 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.


CONCLUSIONS
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 GA1 as early as possible. Several studies suggest that presymptomatic treatment may prevent or postpone the onset of symptoms.
Bjugstad
K B
KB
Division of Clinical Pharmacology and Toxicology, the Department of Medicine, University of Colorado Health Sciences Center, Denver, Colorado 80262, USA.
Goodman
S I
SI
Freed
C R
CR
D017668:Age of Onset; D001284:Atrophy; D001479:Basal Ganglia / Q000473:pathology; D002540:Cerebral Cortex / Q000473:pathology; D002675:Child, Preschool; D018450:Disease Progression; D050770:Glutaryl-CoA Dehydrogenase; D006801:Humans; D007223:Infant; D008661:Metabolism, Inborn Errors / Q000453:epidemiology / Q000503:physiopathology*; D009468:Neuromuscular Diseases / Q000503:physiopathology*; D010088:Oxidoreductases / Q000172:deficiency*; D044925:Oxidoreductases Acting on CH-CH Group Donors; D011379:Prognosis; D012044:Regression Analysis; D012720:Severity of Illness Index; D013346:Subarachnoid Space / Q000473:pathology
D010088:Oxidoreductases; D044925:Oxidoreductases Acting on CH-CH Group Donors; D050770:Glutaryl-CoA Dehydrogenase