• Chin-Tung Hsieh, Wuh-Liang Hwu, Yuan-Te Huang, Ai-Chu Huang, Shiao-Fang Wang, Min-Huei Hu, and Yin-Hsiu Chien.
• Department of Pediatrics, National Taiwan University Hospital and National Taiwan University College of Medicine, Taipei, Taiwan.
• J Formos Med Assoc. 2008 Feb 1; 107 (2): 139144139-44.

Background/PurposeGlutaric aciduria type 1 (GA1) is an inborn error of lysine and tryptophan metabolism. There is a lack of initial diagnostic signs of the disease, but late treatment often results in severe neurologic impairment. In this study, we analyzed the results of screening for GA1 in a Chinese population.MethodsDry blood spots were obtained at about 3 days of age from 357,307 newborns and tested for elevation of glutaryl (C5DC)-carnitine by tandem mass spectroscopy. A second sample of blood spots was required from those cases with abnormal elevation of C5DC-carnitine (higher than the cut-off value) (recall). If the results remained abnormal, those cases were referred for confirmation of the diagnosis and treatment.ResultsBetween August 2001 and February 2005, there were 40 cases with C5DC-carnitine more than 0.13 microM (the cut-off value), from whom a second sample of blood spots was obtained (recall rate, 0.02%); two cases were confirmed to be affected by GA1. Because of the low positive prediction rate using this cut-off value, we elevated the cut-off value slightly. Between February 2005 and August 2006, there were eight cases with C5DC-carnitine more than 0.22 microM from whom a second sample of blood spots was obtained (recall rate, 0.01%); three cases were confirmed to be affected by GA1. All five cases with persistent elevation of C5DC-carnitine were referred and diagnosis was confirmed in each, giving an incidence of 1 in 71,461 newborns. There were no false negatives. Magnetic resonance imaging studies obtained from four cases showed frontotemporal atrophy at the time of diagnosis. Two cases were followed for over 1 year, and under treatment with dietary control and carnitine supplementation, both had normal development and neither exhibited a frank episode of encephalopathic crisis.ConclusionWith properly established cut-offs, GA1 can be successfully screened for in populations with a low incidence of the disease. Early treatment is likely to improve the outcome of cases discovered by screening.

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