摘要
目的了解我国各省（市）、自治区对高苯丙氨酸血症（hyperphenylalaninemia，HPA）患儿进行四氢生物蝶呤缺乏症（tetrahydrobiopterin deficiency，BH4D）鉴别诊断的普及情况及BH4D的发病率。方法选取1993--2007年接受BH4D鉴别诊断的1392例HPA患儿（门诊591例，递送标本801例）为研究对象。根据门诊及实验室资料统计BH4D鉴别诊断的病例数，探讨诊断标准，得出BH4D发病率及高发地区。结果（1）近3年尿蝶呤谱分析及红细胞二氢蝶啶还原酶（dihydropteridine reductase，DHPR）活性测定的病例数明显递增，2005年2项试验的病例数分别为217例和198例，至2007年病例数分别达到511例和458例，病例总数约为2005年的2．3倍，覆盖全国29个省（市）、自治区；（2）尿生物蝶呤及生物蝶呤百分比是诊断6－丙酮酰四氢蝶呤合成酶缺乏症（6-pyruvoyl tetrahydropterinsynthase deficiency，PTPSD）的关键指标，96．83％（61／63）PTPSD患儿尿生物蝶呤百分比〈5％[（1．41±1．10）％]，生物蝶呤极低[（0．14±0．17）mmol／mol肌酐]；四氢生物蝶呤（BH4）负荷试验2～6h血苯丙氨酸浓度降至正常有助于诊断；DHPR活性降低是DHPR缺乏症的确诊方法；（3）1392例HPA患儿中PTPSD及DHPR缺乏症的发病率分别为8．41％（117／1392）和0．18％（2／1108）；80％（8／10）的高发省（市）、自治区位于我国的华东及南部；上海PTPSD在HPA患儿及新生儿群体中发病率分别为10．81％（8／74）和0．007‰（8／1121429）。结论近3年我国大部分省（市）、自治区临床医生开展BH4D鉴别诊断的意识明显提高；BH4D在HPA患儿中的发病率至少为8．55％（119／1392），PTPSD占98．32％（117／119）。
Objective To investigate the development of differential diagnosis of tetrahydrobiopterin （BH4） deficiency among patients with hyperphenylalaninemia（HPA） in provinces or cities of China and to investigate the incidence of BH4 deficiency. Methods Of the thirteen hundreds and ninety-two patients with HPA received, the differential diagnosis for BH4 deficiency during 1993 -2007 were enrolled in this study. Of which,591 patients came from outpatient and 801 patients＇ samples from other provinces or cities were sent to author＇s laboratory to investigate the case number of differential diagnosis for BH4 deficiency in provinces or cities of China according to the data from both outpatient case histories and laboratory as to investigating the development of differential diagnosis in the whole country. To discuss the diagnostic criteria for BH4 deficiency was according to the results of urinary pterin analysis, determination of dihydropteridine reductase（DHPR） activity and the tetrahydrobiopterin loading test as well as to get the incidence of BH4 deficiency and find some provinces or cities with higher incidence of BH4 deficiency in China.Results （ 1 ） The number of HPA patients, who were performed by urinary pterin analysis and the determination of DHPR activity, were remarkably increased in last three years （ 2005 - 2007 ）. The patient numbers of both urinary pterin analysis and DHPR activity determination were 217 and 198 respectively in 2005. And in 2007 they increased to 511 and 458, which was about 2.3 times than that in 2005. The patients came from 29 provinces or cities in 2007. （2） The urinary biopterin and biopterin percent were key marks for diagnosis of 6-pyruvoyl tetrahydropterin synthase （PTPS） deficiency. The less than 5% [ （ 1.41 ± 1.10） % ] biopterin percent and very low biopterine level [ （0. 14 ± 0. 17 ） mmol/mol Cr] were found in 96. 83% （ 61/63 ） patients with PTPS deficiency in this study. The blood phenylalanine level was remarkably decreased to normal range at 2 -6 hours after BH4 loading test. The very low DHPR activity was a final diagnostic mark for DHPR deficiency. The very low DHPR activities of 0. 27 nmol/（ min · 5 mm disc） （6. 11% -7.00% of normal controls） were found in two patients with DHPR deficiency in this study. （3） The incidences of PTPS deficiency and DHPR deficiency among 1392 patients with hyperphenylalaninemia were 8.41% （117/1392） and 0. 18% （2/1108） respectively. About 67. 23% （80/119） patients with BH4 deficiency came from the south of Yangtze liver. The 80% （8/10） provinces or cities with higher incidence of BH4 deficiency are located in eastern and southern China. The incidence of PTPS deficiency among patients with HPA and normal newborns was 10. 81% （ 8/74 ） and 0. 007‰ （ 8/1 121 429 ） respectively in Shanghai, China according to data from neonatal screening. Conclusion The awareness of differential diagnosis for BH4 deficiency from clinic pediatricians has been increased in most provinces or cities of China in last three years, but it should be more strengthened.
出处
《中华预防医学杂志》
CAS
CSCD
北大核心
2009年第2期128-131,共4页
Chinese Journal of Preventive Medicine
基金
国家“863”高技术研究发展计划（2007AA02Z447）
“十一五”国家科技支撑计划项目（2006BA105A05,2006BA105A07）
上海市重点学科建设项目（T0204）
关键词
苯丙酮尿症
生物蝶呤
缺乏症
新生儿筛查
Phenylketonurias
Biopterin
Deficiency disease
Neonatal screening
