Wen Peng -qiang, Wang Guo-bing, Liu Xiao-hong, Chen Zhan-ling, Shang Yue, Cui Dong, Song Ping, Yuan Quan, Chen Shu-li, Liao Jian-xiang, Li Cheng-rong
Shenzhen Institute of Pediatrics, Shenzhen Children's Hospital, Shenzhen, Guangdong 518026, PR China.
Zhonghua Yi Xue Yi Chuan Xue Za Zhi. 2012 Dec;29(6):642-7. doi: 10.3760/cma.j.issn.1003-9406.2012.06.004.
To review clinical features of four male patients with glutaric academia type I and screen glutaryl-CoA dehydrogenase (GCDH) gene mutations.
The 4 patients underwent brain computer tomography (CT) and magnetic resonance imaging (MRI) analyses. Blood acylcarnitine and urine organic acid were analyzed with tandem mass spectrometry and gas chromatographic mass spectrometry. Genomic DNA was extracted from peripheral blood samples. The 11 exons and flanking sequences of GCDH gene were amplified with PCR and subjected to direct DNA sequencing.
All patients have manifested macrocephaly, with head circumference measured 50 cm (14 months), 47 cm (9 months), 46 cm (5 months) and 51 cm (14 months), respectively. Imaging analyses also revealed dilation of Sylvian fissure and lateral ventricles, frontotemporal atrophy, subarachnoid space enlargement and cerebellar vermis abnormalities. All patients had elevated glutarylcarnitine (5.8 umol/L, 7.5 umol/L, 8.3 umol/L and 7.9 umol/L, respectively) and high urinary excretion of glutaric acid. Seven mutations were identified among the patients, among which c.146_149del4, IVS6-4_Ex7+4del8, c.508A>G (p.K170E), c.797T>C (p.M266T) and c.420del10 were first discovered.
Macrocephaly and neurological impairment are the most prominent features of glutaric academia type I. Blood tandem mass spectrometry and urine gas chromatographic mass spectrometry analysis can facilitate the diagnosis. The results can be confirmed by analysis of GCDH gene mutations.
回顾4例I型戊二酸血症男性患者的临床特征并筛查戊二酰辅酶A脱氢酶（GCDH）基因突变。
4例患者接受了脑部计算机断层扫描（CT）和磁共振成像（MRI）分析。采用串联质谱法和气相色谱 - 质谱法分析血酰基肉碱和尿有机酸。从外周血样本中提取基因组DNA。用聚合酶链反应（PCR）扩增GCDH基因的11个外显子及其侧翼序列，并进行直接DNA测序。
所有患者均表现为巨头畸形，头围分别为50 cm（14个月）、47 cm（9个月）、46 cm（5个月）和51 cm（14个月）。影像学分析还显示大脑外侧裂和侧脑室扩张、额颞叶萎缩、蛛网膜下腔增宽以及小脑蚓部异常。所有患者的戊二酰肉碱均升高（分别为5.8 μmol/L、7.5 μmol/L、8.3 μmol/L和7.9 μmol/L），尿中戊二酸排泄量高。在患者中鉴定出7种突变，其中c.146_149del4、IVS6 - 4_Ex7 + 4del8、c.508A>G（p.K170E）、c.797T>C（p.M266T）和c.420del10为首次发现。
巨头畸形和神经功能障碍是I型戊二酸血症最突出的特征。血串联质谱分析和尿气相色谱 - 质谱分析有助于诊断。GCDH基因突变分析可证实结果。
