Hsieh Chin-Tung, Hwu Wuh-Liang, Huang Yuan-Te, Huang Ai-Chu, Wang Shiao-Fang, Hu Min-Huei, Chien Yin-Hsiu
Department of Pediatrics, National Taiwan University Hospital and National Taiwan University College of Medicine, Taipei, Taiwan.
J Formos Med Assoc. 2008 Feb;107(2):139-44. doi: 10.1016/S0929-6646(08)60127-8.
BACKGROUND/PURPOSE: Glutaric 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.
Dry 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.
Between 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.
With 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.
背景/目的：1型戊二酸血症（GA1）是赖氨酸和色氨酸代谢的一种先天性缺陷。该病缺乏早期诊断体征，但治疗延迟常导致严重的神经功能损害。在本研究中，我们分析了中国人群中GA1的筛查结果。
从357307名新生儿出生后约3天时采集干血斑，采用串联质谱法检测戊二酰基（C5DC）-肉碱水平是否升高。对于C5DC-肉碱水平异常升高（高于临界值）的病例（召回），需要采集第二份血斑样本。如果结果仍异常，则将这些病例转诊以确诊和治疗。
2001年8月至2005年2月，有40例C5DC-肉碱水平超过0.13微摩尔（临界值），从中采集了第二份血斑样本（召回率为0.02%）；2例确诊为GA1。由于使用该临界值时阳性预测率较低，我们将临界值略微提高。2005年2月至2006年8月，有8例C5DC-肉碱水平超过0.22微摩尔，从中采集了第二份血斑样本（召回率为0.01%）；3例确诊为GA1。所有5例C5DC-肉碱持续升高的病例均被转诊并确诊，新生儿发病率为1/71461。无假阴性。4例患者的磁共振成像研究显示诊断时存在额颞叶萎缩。2例随访超过1年，在饮食控制和补充肉碱治疗下，两者发育正常，均未出现明显的脑病危机发作。
通过适当设定临界值，GA1可在该病低发病率人群中成功筛查。早期治疗可能改善筛查发现病例的预后。
