福建地区三例戊二酸血症Ⅰ型患儿GCDH基因的突变分析

Analysis of GCDH gene mutations in 3 patients from Fajian area with glutaric academia type Ⅰ

目的探讨福建地区3例戊二酸血症Ⅰ型患儿基因突变的类型及其临床特点。方法对3例患儿进行串联质谱及气相质谱检查，同时进行磁共振检查，提取外周血基因组DNA，针对戊二酰辅酶A脱氢酶（glutaric-CoA dehydrogenenaes，GCDH）基因的12个外显子及其侧翼序列进行Sanger测序。结果3例患儿均存在GCDH基因突变，1例为c．1244-2A〉C、c．1147C〉T（p．R383C）复合杂合突变，1例为c．1244-2A〉C纯合突变，1例为c．406G〉T（p．G136C）、c．1169G〉A（p．G390E）复合杂合突变。100名正常对照未见相同的突变。3例患儿中仅1例进行了新生儿疾病筛查并及早得到了干预，至今未发病。其余2例由于发现延迟，对智力造成了不可逆的损伤。结论在发现的3例病例中，其中c．1169G〉A（p．G390E）为中国人群中新发现的GCDH可能致病突变类型。早期进行新生儿遗传代谢病筛查具有重要的意义。

Objective To explore clinical features and mutation types in patients from Fujian area with glutaric academia type Ⅰ（GA Ⅰ ）. Methods Serum acylcarnitine and urine organic acid of 3 patients were determined with tandem mass spectrometry and gas chromatographic mass spectrometry. The patients also underwent magnetic resonance imaging analysis for the cranial region. Genomic DNA was extracted from peripheral blood samples, and the 12 exons and flanking regions of the GCDH gene were amplified with PCR and subjected to direct DNA sequencing. One hundred healthy newborns were used as controls. Results Mutations of the GCDH gene were identified in all of the 3 patients. Two patients have carried compound heterozygous mutations including c. 1244-2A〉C and c. l147C〉T（p. R383C）, c. 406G〉T （p. G136C） and c. l169G〉A（p. G390E）, respectively. One has carried homozygous c. 1244-2A〉C mutation. The same mutations were not detected among the 100 healthy newborns. Only one patient received early intervention and did not develop the disease. The other two had irreversible damagesto their intelligence. Conclusion c. l169G〉A（p. G390E） is likely pathogenic mutations for GA Ⅰ patients from Fujianarea. Early screening of neonatal metabolic diseases is crucial for such patients.