Neonatal hyperphenylalaninemia screening from 1985 to 2012 in Nanjing: a retrospective analysis of 27 years

Abstract

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. Key words: Phenylketonurias; phenylalanine hydroxylase; Mutation; Neonatal screening; Retrospective studies