四氢生物蝶呤缺乏症的快速诊断、治疗与随访

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1、上海交通大学硕士学位论文四氢生物蝶吟缺乏症的快速诊断、治疗与随访姓名：顾梅青申请学位级别：硕士专业：儿科学指导教师：叶军20080401R221X突变导致严重型临床表型。（4）BH4缺乏症血（生物蝶吟+蝶吟）%明显低于正常对照组（7=6.350,P=0.000）,符合诊断；1例正常人血各蝶吟浓度的实验批内CV（3〜11%）,批间CV（19〜23%）o结论（1）对所有HPA患儿及早进行BH4缺乏症鉴别诊断，3个月内治疗可改善预后；（2）P87S、N52S、D96N及IVSlnt-291A>G为中国人PTS热点突变,PCR-RFLP提高基因诊断效率；（3）干血滤纸片蝶吟谱分析方法有望代替尿蝶吟谱进

2、行BH4缺乏症诊断。关键词四氢生物蝶吟缺乏症，高苯丙氨酸血症，基因突变，高效液相色谱法THEFASTDIAGNOSIS^TREATMENTANDFOLLOW-UPOFTETRAHYDROBIOPTERINDEFICIENCYABSTRACTObjectiveToemphasizetheimportanceofdifferentialdiagnosisofBH4deficiencyinpatientswithhyperphenylalaninemia・ToacquirethegenemutationspectrumofChineseandevaluatetheoutcomeaftertreatm

3、ent.TomakeitpossiblethatallthetestsforthediagnosisofBH4deficiencycanbecompletedonlybyusingdriedbloodspotsonfilterpaper.Method(1)FastdiagnoseBH4deficiencybypterinsanalysisinurine,measurementofdihydropteridineactivityandBH4loadingtest.(2)DeterminegenemutationsofBH4deficiencybymeansofPCR-RFLPandotherte

4、chniques・(3)AdministrateBH4andneurotransmitterprecursorsandevaluatetherapeuticeffect.(4)Developthemethodforpterinsanalysisindriedbloodspotsonfilterpaperandestablishreferencevalues・Andevaluatetheapplicationperspective.Results(1)73BH4deficientpatients,including716-pyruvoyltetrahydrobiopterinsynthesisd

5、eficiecy(97.26%)and2dihydropteridinereductasedeficiency(2.74%),outof640HPAwerediagnosedandtheincidenceis11.41%.(2)18mutationtypesofPTSgenewereidentified.TheP87S(40.91%)>N52S(13.64%)、D96N(11.82%)andIVSlnt-291A>G(10%)mutationsaccountedforabout76.36%ofthemutantalleles.TheP87Lmutationwasreportedfdrthefi

6、rsttimeinChineseMainland.TheQ13X>M80T、IVS4nt-2A>G>L93M、L127F、K131Nmutationswerenovel.TheR221XmutationandtwonovelmutationsnamedP172LandC104YwerefoundinQDPRgene.(3)96.43%ofthosewhoreceivetherapywithin3monthsafterbirthhavenormalintellectualdevelopment.Thepercentagewashigherthanthosewhoreceiveddelayedtr

7、eatmentobviously.About89%ofPTSgenemutationsandtheP172LandR221XmutationsofQDPRgenewereassociatedwithseverephenotype・(3)(Biopterin+pterin)%inboodspotsislowerthanthatinurinobviously(1=6.350，P=0.000),inac