Study on 398 neonates with various types of hyperphenylalaninemia detected by neonatal screening program and 26 year-experiences of diagnosis and treatment for hyperphenylalaninemia

Abstract

Objective To investigate the incidences of various types of hyperphenylalaninemia (HPA)detected by neonatal screening program from 1981 to 2007,and provide the 26 year-experiences of diagnosis,treatment and prognosis for HPA.Methods The differential diagnosis for all patients with HPA has been performed by BH4 loading test,urinary pterin and dihydropteridine reductase activity determination.Analyze the relationship between mental developments and blood phenylalanine(Phe)levels.PAH gene mutations were tested by DNA analyze also.Results (1)85.9%patients(342/398)were diagnosed as phenylalanine hydroxylase deficiency(PAHD),36.7%(146/398)were diagnosed as BH4 responsive PAHD,and 66.5% patients with BH4 responsive PAHD were found in mild phenyIketonuria(MPKU)and mild HPA(MHPA).14.1%patients(56/398)diagnosed as BH4 deficiency,including 55 patients(98.2%)with 6-pyruvoyl-tetrahydropterin synthase deficiency(PTSD)and one patient with DHPR deficiency.(2)Two hundreds and seventy patients of 398 were followed up.Two hundred and forty-one patients were treated.Thirty-five patients with PTSD were treated with BH4,Levodopa and 5-hydroxytryptophan.Their Phe level were (90±60)mmol/L,the percentage of ideal Phe levels were(97.2±8.1)%.Twenty-one patients with BH4 responsive PAHD received the treatment with single BH4 with average blood Phe levels (180±90)mmol/L.One hundred and eighty-five patients were treated with low/free-phenylalanine formula.their average Phe levels were(336±198)mmol/L,the percentage of ideal Phe levels were only(53±30)%.Twenty seven patients without treatment were had normal mental development with Phe levels(156±42)mmol/L.(3)All 241 treated patients had normal growth development and good nutrition.The positive correlation was found between IQ scores(84±19)and the percentage of ideal Phe levels[(56±33)%](r=0.406,P＜0.01),the negative correlation between IQ and average Phe levels[(348±222)mmol/L]was showed in 62 patients(r=-0.406,P＜0.01).(4)Nineteen kinds of PTS gene mutations were found in 31 patients with PTSD,and the mutations of 259C＞T(48.3%)and 286G＞A(15.5%)were the most common.Seven kinds of PAH gene mutations were found in 13 Datients with BH4 responsive PAHD and R241C(43.8%)was the common mutation.Conclusions All HPA patients should be quickly differential diagnosed before treatment.Phe level control is a very key factor for mental development in treatment. Key words: Hyperphenylalaninemia; phenylalanine hydroxylase; tetrahydrobiopterin; neonatalscreening; intelligence quotient