Tang N L, Hui J, Law L K, Lam Y Y, Chan K Y, Yeung W L, Chan A Y, Cheung K L, Fok T F
Department of Chemical Pathology, The Chinese University of Hong Kong.
Hum Mutat. 2000 Nov;16(5):446. doi: 10.1002/1098-1004(200011)16:5<446::AID-HUMU14>3.0.CO;2-Y.
Glutaric acidemia type I is caused by mutations of the glutaryl-CoA dehydrogenase (GCDH) gene resulting in loss of GCDH enzyme activity. Patients present with progressive dystonia and lesions in basal ganglia. Dietary treatment, when instituted from the early neonatal period, markedly reduces dystonia and morbidity. Early diagnosis and prenatal diagnosis will be facilitated by knowledge of locally prevalent GCDH mutations. Several common GCDH mutations have been found in different ethnic groups. GCDH mutations were studied in 5 Chinese glutaric acidemia type I families. We detected two novel recurrent mutations (A219T and IVS10-2A>C) which were found in two unrelated families. An asymptomatic carrier of IVS10-2A>C was also found on screening of 120 individuals. Other mutations were identified, including two other novel (R386G & IVS3+1G>A) and two known mutations (G178R & R355H). Fibroblasts from patients carrying the novel mutations were confirmed to be deficient for GCDH activity. This is the first report of GCDH mutations describing recurrent mutations in Chinese patients. The carrier rate of IVS10-2A>C may be particularly high in Chinese.
I型戊二酸血症由戊二酰辅酶A脱氢酶（GCDH）基因突变引起，导致GCDH酶活性丧失。患者表现为进行性肌张力障碍和基底神经节病变。若从新生儿早期开始进行饮食治疗，可显著降低肌张力障碍和发病率。了解当地常见的GCDH突变将有助于早期诊断和产前诊断。在不同种族群体中已发现几种常见的GCDH突变。对5个中国I型戊二酸血症家庭的GCDH突变进行了研究。我们检测到两个新的复发性突变（A219T和IVS10-2A>C），这两个突变出现在两个无亲缘关系的家庭中。在对120人进行筛查时还发现了一名IVS10-2A>C的无症状携带者。还鉴定出了其他突变，包括另外两个新突变（R386G和IVS3+1G>A）以及两个已知突变（G178R和R355H）。携带新突变的患者的成纤维细胞被证实GCDH活性缺乏。这是关于GCDH突变的首次报告，描述了中国患者中的复发性突变。IVS10-2A>C在中国的携带率可能特别高。
