戊二酸血症Ⅰ型患儿62例临床表现及质谱检测结果分析

Analysis of clinical features and the results of mass spectrometry with glutaric acidemia type I

目的 对戊二酸血症Ⅰ型（glutaric acidemia type Ⅰ，GA-Ⅰ）患儿临床表现及质谱检测结果进行分析，探讨质谱检测技术对GA-Ⅰ的诊断价值，有助于提高临床医生对该病的认识。方法 回顾性分析2007年12月至2016年4月确诊的62例患儿临床资料，另设62名健康儿童为对照组。串联质谱检测血游离肉碱（C0）、戊二酰肉碱（C5DC）、辛酰肉碱（C8）水平及C5DC/C8值，气相色谱质谱检测尿戊二酸、甲羟戊酸内酯水平。46例患儿行基因突变检测。结果 确诊GA-Ⅰ患儿62例，其中男童36例，女童26例，首诊年龄中位数1.2岁，主要表现为头大畸形、运动障碍、抽搐等。患儿血C0、C8、C5DC、C5DC/C8、尿戊二酸、甲羟戊酸内酯水平中位数分别为20.00 μmol/L、0.04 μmol/L、0.90 μmol/L、24.25、936.30 mmol/mol肌酐和141.5 mmol/mol肌酐，除血C0、C8外均显著高于对照组（均P〈0.01）。头颅核磁共振（MRI）检查34例，主要表现为脑白质病变、额颞部脑外间隙及外侧裂池异常增宽等。结论 头大畸形、运动障碍、智力落后或倒退、反复抽搐、头颅MRI特征性异常改变是GA-Ⅰ的主要临床表现；尿戊二酸及血C5DC、C5DC/C8增高对诊断GA-Ⅰ具有特异性，诊断GA-Ⅰ需将两种检测方法结合以减少漏诊及误诊。尿戊二酸及血C5DC/C8轻度增高者需反复送检或基因检测确诊。

Objective For clinically understanding of glutaric acidemia type I （ GA- I ） , the relationship of the clinical manifestations and the serum levels of free earnitine （CO）, glutarylearuitine （C5DC）, and eapryloylcarnitine （ C8 ） as well as the urinary levels of glutaric acid and mevalonolactone of patients with GA- ] were studied. Methods From December 2007 to April 2016, a total of 62 patients with GA- I （ GA- I group） and 62 healthy children （ control group） were included. Tandem mass spectrometry was used to measure the blood levels of CO, C5DC, and C8, while, gas chromatography-mass spectrometry was used to measure the urine levels of glutaric acid and mevalonolactone. Results Total 62 cases, 36 males and 26 females, median age 1.2 years （ range from 27 days to 9.3 years） were enrolled. Clinical features included macrocephaly, dyskinesia, seizures, growth and mental retardation, abnormal muscular tension, as well as feeding difficulties. The median levels of C5DC, C5DC/C8, glutaric acid, mevalonolaetone were 0.90 p, mol/L, 24.25, 936. 30 mmol/mol creatinine, and 141.5 mmool/tool creatinine respectively, which were higher than those of the control group （ all P〈0.01 ）. While the median level of CO was between the reference value, and the median level of C8 was lower than the control group （0.04 vs 0.10 mmol/L）. Cranial magnetic resonance image （MRI） had been carried out in 34 patients. Multiple and symmetrical abnormal signal in white matter and basal ganglia, widening of the sylvian fissure, expansion of cerebro-spinal fluid spaces anterior to the temporal lobes were cardinal signs of GA- I - Conclusions Patients with GA- I present with complex and variable clinical features, mainly including abnormal increase of head circumference, retarded motor and language development, repeated convulsions and characteristic abnormalities in brain MRI. Significant increase in the blood levels of C5DC and C5DC/C8 and in urine level of glutaricacid and mevalonolactonemay are specific to the diagnosis of GA- I. For mild cases, repeated tests and genomic mutation analysis are necessary.