苯丙酮尿症质谱筛查和基因诊断分析

Phenylketonuria Mass Spectrometry Screening and Genetic Diagnosis Analysis

目的探讨苯丙酮尿症患儿的代谢筛查情况、基因突变特点及诊治经验。方法 2016年1月—2017年4月,通过该院DNA分型中心筛查的3 593例高危儿相关实验室检查(血液氨基酸和酰基肉碱检测、尿液有机酸检测和基因诊断)结果确诊的8例PKU患者,并结合近年来国内文献资料进行复习。结果 8例患儿中男3例,女5例;发病年龄72 h～20 d;血液氨基酸和肉碱检测显示8例Phe值显著大于正常值120μM;尿液有机酸检测显示只有两例明显出现苯乙酸的积累;基因诊断结果显示8例共检测出7种突变:c.442-1G>A、c.721C>T、 c.728G>A、c.781C>T、c.1238G>C、c.1256A>G和c.1301G>A。结论遇到新生儿苯丙酮尿症和先天性甲状腺功能减低症普筛中异常的患儿,需要注意排除,避免假阳性结果,血液氨基酸和肉碱检测、尿液有机酸检测和基因诊断是其主要诊断指标;早期发现、早期诊断后饮食控制对病情十分有利。

Objective To investigate the metabolic screening, gene mutation characteristics and diagnosis and treatment of children with phenylketonuria. Methods From January 2016 to April 2017, 3593 high-risk children related laboratory tests(blood amino acid and acylcarnitine test, urine organic acid test and genetic diagnosis) were screened by our DNA typing center. 8 patients with PKU were reviewed in conjunction with recent domestic literature. Results Of the 8patients, 3 were male and 5 female; the age of onset was 72 h to 20 d; blood amino acid and carnitine test showed that 8 Phe values were significantly greater than the normal value of 120 μM; urine organic acid test showed only two cases.The accumulation of phenylacetic acid appeared obviously; the results of gene diagnosis showed that 7 mutations were detected in 8 cases: c.442-1G>A, c.721C>T, c.728G>A, c.781C>T, c.1238G> C, c.1256A>G and c.1301G>A. Conclusion Children with abnormalities in neonatal phenylketonuria and congenital hypothyroidism need to be carefully excluded to avoid false positive results, blood amino acids Carnitine testing, urine organic acid testing and genetic diagnosis are the main diagnostic indicators; early detection, early diagnosis and diet control is very beneficial to the condition.