中华围产医学杂志
中華圍產醫學雜誌
중화위산의학잡지
CHINESE JOURNAL OF PERINATAL MEDICINE
2013年
6期
357-361
,共5页
孙云%蒋涛%张菁菁%孙亦骏%陈玉林%杨冰%张瑾%黄美莲%张晓娟
孫雲%蔣濤%張菁菁%孫亦駿%陳玉林%楊冰%張瑾%黃美蓮%張曉娟
손운%장도%장정정%손역준%진옥림%양빙%장근%황미련%장효연
苯丙酮尿症%苯丙氨酸羟化酶%突变%新生儿筛查%回顾性研究
苯丙酮尿癥%苯丙氨痠羥化酶%突變%新生兒篩查%迴顧性研究
분병동뇨증%분병안산간화매%돌변%신생인사사%회고성연구
Phenylketonurias%phenylalanine hydroxylase%Mutation%Neonatal screening%Retrospective studies
目的 了解南京地区新生儿高苯丙氨酸血症的发生率、分型、治疗及预后.方法 本研究为回顾性研究.选择1985年9月1日至2012年9月1日共27年在南京地区出生的新生儿,在新生儿出生72h已充分哺乳后采集足跟血,于新生儿出生后20 d内由南京市新生儿疾病筛查中心采用荧光定量法测定血苯丙氨酸浓度.对确诊高苯丙氨酸血症的81例患儿进行四氢生物蝶呤负荷试验、尿蝶呤谱分析和红细胞二氢蝶啶还原酶活性测定以鉴别诊断.治疗随访期间定期监测血苯丙氨酸浓度与智能发育水平,并进行苯丙氨酸羟化酶基因突变分析.采用方差分析、LSD法和Pearson相关性分析等统计学方法研究血苯丙氨酸浓度与智能发育的关系.结果 (1)南京地区新生儿高苯丙氨酸血症的发生率为1/8800(81/712 818),确诊的81例高苯丙氨酸血症患儿中苯丙氨酸羟化酶缺乏症78例(96.3％),其中经典型苯丙酮尿症37例,轻度苯丙酮尿症23例,轻度高苯丙氨酸症18例；四氢生物蝶呤缺乏症3例(3.7％),均为6-丙酮酰四氢蝶呤合成酶缺乏症.(2)81例高苯丙氨酸血症患儿中8例放弃治疗,其中2例死亡,6例患儿均存在不同程度的智能发育落后,1例合并癫痫；6例治疗过程中失访；坚持治疗的67例高苯丙氨酸血症患儿末次随访年龄为3个月～26岁.55例接受智能发育评估的患儿中5例患儿智能发育异常(智商＜75分).(3)智能发育水平与血苯丙氨酸控制浓度呈负相关(r=-0.53,P＜0.05),与血苯丙氨酸初始浓度无相关性(r=-0.39,P＞0.05).(4) 20例接受苯丙氨酸羟化酶基因突变分析患儿共携带18种PAH基因突变,其中突变频率最高的为EX6-96A＞G和R241C(34.28％).结论 南京地区新生儿高苯丙氨酸血症的发生率高于全国平均水平.早期诊断并规范治疗的患儿90％以上智能发育正常.南京地区PAH基因的突变热点为EX6-96A＞G和R241C,与其他地区有所不同.
目的 瞭解南京地區新生兒高苯丙氨痠血癥的髮生率、分型、治療及預後.方法 本研究為迴顧性研究.選擇1985年9月1日至2012年9月1日共27年在南京地區齣生的新生兒,在新生兒齣生72h已充分哺乳後採集足跟血,于新生兒齣生後20 d內由南京市新生兒疾病篩查中心採用熒光定量法測定血苯丙氨痠濃度.對確診高苯丙氨痠血癥的81例患兒進行四氫生物蝶呤負荷試驗、尿蝶呤譜分析和紅細胞二氫蝶啶還原酶活性測定以鑒彆診斷.治療隨訪期間定期鑑測血苯丙氨痠濃度與智能髮育水平,併進行苯丙氨痠羥化酶基因突變分析.採用方差分析、LSD法和Pearson相關性分析等統計學方法研究血苯丙氨痠濃度與智能髮育的關繫.結果 (1)南京地區新生兒高苯丙氨痠血癥的髮生率為1/8800(81/712 818),確診的81例高苯丙氨痠血癥患兒中苯丙氨痠羥化酶缺乏癥78例(96.3％),其中經典型苯丙酮尿癥37例,輕度苯丙酮尿癥23例,輕度高苯丙氨痠癥18例；四氫生物蝶呤缺乏癥3例(3.7％),均為6-丙酮酰四氫蝶呤閤成酶缺乏癥.(2)81例高苯丙氨痠血癥患兒中8例放棄治療,其中2例死亡,6例患兒均存在不同程度的智能髮育落後,1例閤併癲癇；6例治療過程中失訪；堅持治療的67例高苯丙氨痠血癥患兒末次隨訪年齡為3箇月～26歲.55例接受智能髮育評估的患兒中5例患兒智能髮育異常(智商＜75分).(3)智能髮育水平與血苯丙氨痠控製濃度呈負相關(r=-0.53,P＜0.05),與血苯丙氨痠初始濃度無相關性(r=-0.39,P＞0.05).(4) 20例接受苯丙氨痠羥化酶基因突變分析患兒共攜帶18種PAH基因突變,其中突變頻率最高的為EX6-96A＞G和R241C(34.28％).結論 南京地區新生兒高苯丙氨痠血癥的髮生率高于全國平均水平.早期診斷併規範治療的患兒90％以上智能髮育正常.南京地區PAH基因的突變熱點為EX6-96A＞G和R241C,與其他地區有所不同.
목적 료해남경지구신생인고분병안산혈증적발생솔、분형、치료급예후.방법 본연구위회고성연구.선택1985년9월1일지2012년9월1일공27년재남경지구출생적신생인,재신생인출생72h이충분포유후채집족근혈,우신생인출생후20 d내유남경시신생인질병사사중심채용형광정량법측정혈분병안산농도.대학진고분병안산혈증적81례환인진행사경생물접령부하시험、뇨접령보분석화홍세포이경접정환원매활성측정이감별진단.치료수방기간정기감측혈분병안산농도여지능발육수평,병진행분병안산간화매기인돌변분석.채용방차분석、LSD법화Pearson상관성분석등통계학방법연구혈분병안산농도여지능발육적관계.결과 (1)남경지구신생인고분병안산혈증적발생솔위1/8800(81/712 818),학진적81례고분병안산혈증환인중분병안산간화매결핍증78례(96.3％),기중경전형분병동뇨증37례,경도분병동뇨증23례,경도고분병안산증18례；사경생물접령결핍증3례(3.7％),균위6-병동선사경접령합성매결핍증.(2)81례고분병안산혈증환인중8례방기치료,기중2례사망,6례환인균존재불동정도적지능발육락후,1례합병전간；6례치료과정중실방；견지치료적67례고분병안산혈증환인말차수방년령위3개월～26세.55례접수지능발육평고적환인중5례환인지능발육이상(지상＜75분).(3)지능발육수평여혈분병안산공제농도정부상관(r=-0.53,P＜0.05),여혈분병안산초시농도무상관성(r=-0.39,P＞0.05).(4) 20례접수분병안산간화매기인돌변분석환인공휴대18충PAH기인돌변,기중돌변빈솔최고적위EX6-96A＞G화R241C(34.28％).결론 남경지구신생인고분병안산혈증적발생솔고우전국평균수평.조기진단병규범치료적환인90％이상지능발육정상.남경지구PAH기인적돌변열점위EX6-96A＞G화R241C,여기타지구유소불동.
Objective To explore the incidence,classification,treatment and prognosis of neonatal hyperphenylalaninemia(HPA) in Nanjing.Methods Infants born from September 1st,1985 to September 1st,2012 in Nanjing were investigated.Heel blood samples of neonates were collected at 72 hours after birth,and the concentration of blood phenylalanine was determined by fluorescent quantitative method in Nanjing Neonatal Screening Center within 20 days after birth.The deferential diagnosis was performed in all 81 cases diagnosed as HPA by tetrahydrobiopterin loading test,urinary pterin analysis and dihydropteridine reductase activity determination.The blood phenylalanine concentration and mental development were followed up regularly on infants with HPA.Mutations of phenylalanine hydroxylase (PAH) gene were analyzed by gene sequencing in 20 patients with PAH deficiency.The relationship between phenylalanine concentration and mental development was analyzed by variance analysis,LSD and Pearson correlation analysis.Results (1) The incidence of HPA in neonates in Nanjing was 1/8800(81/712 818).Among 81 confirmed cases,78 cases (96.3％) suffered from PAH deficiency,including 37 classical phenylketonurias (PKU),23 mild PKU and 18 mild HPA; the three patients (3.7％) with tetrahydrobiopterin deficiency were all 6-pyruvoyl tetrahydropterin synthase deficiency.(2) Among these 81 cases,eight refused to any treatment (two of them died),six had mental retardation (one with epilepsy),and six were lost in follow-up.For the rest 67 patients who received medical treatment,the ages at the last visit were three months to 26 years old.Among the 55 patients who received mental development evaluation,five of them were abnormal [intelligence quotient (IQ)＜75].(3) Negative correlation was observed between IQ and the average concentration of phenylalanine(r=-0.53,P＜0.05),while no correlation between IQ and the initial concentration of phenylalanine was observed (r =-0.39,P＞0.05).(4)Among the 20 patients with PAH deficiency who were tested for gene sequencing,18 mutations of PAHgenewere detected.The most common mutation were EX6-96A＞G and R241C(34.28％).Conclusions The incidence of HPA in Nanjing was higher than the average national level.With early diagnosis and standard treatment,over 90％ of HPA patients could have normal mental development.The mutation spectrum of PAH gene of Nanjing population is different from other areas,and the most common mutations of PAH gene are EX6-96A＞G and R241C.
