RESUMO
Objective To study the characteristics of hyperphenylalaninemia (HPA) and the differences in blood and urine metabolic index and their correlation.Methods A total of 137 patients with HPA diagnosed by the Pediatric Inherit Metabolism and Endocrine Department,Guangdong Women and Children's Hospital,Guangzhou Medical University from January 2014 to June 2017,were enrolled.Tandem mass spectrometry (MS/MS),gas chromatography/ mass spectrometry (GC-MS) and high performance liquid chromatography (HPLC) were used to analyze the concentration of blood and urine metabolites in children,and the patients were divided into different groups according to the drug load test of tetrahydrobiopterin (BH4) and dihydrobiopterindine reductase (DHPR) deficiency.The HPA metabolite analysis of horizontal concentration by statistical differences and correlation analysis were performed.Results Among the 137 cases of HPA,there were 101 cases (73.7%) of phenylalanine hydroxylase deficiency (PAH),and among them 21 cases (15.3%) were classic phenylketonuria (PKU),37 cases were mild PKU (27.0%),43 cases (31.4%) wcrc mild HPA.Thcrc were 22 cases (16.1%) with BH4 reaction,and 79 cases (57.7%) of non-reactive type.Besides,there were 36 cases (26.3%) of tetrahydrobiopterin deficiency (BH4 D),of which 6-pyruvoyl tetrahydropterin synthase deficiency (PTPS) in 34 cases (24.8%) and dihydrobiopterindine reductase deficiency (DHPR) in 2 cases (1.5%).Urinary phenylacetic acid (r =0.673,P < 0.01),phenyllactic acid (r =0.736,P < 0.01),phenylpyruvic acid (r =0.642,P < 0.01) were significantly correlated with blood phenylalanine (Phe) concentration,and the neopterin (N) (r =0.442,P < 0.01) and biopterin (B) (r =0.398,P < 0.01) had low correlation.Urinary phenylacetic acid,phenyllactic acid and phenylpyruvic acid had no correlation with urinary pterin.There were significant differences among PTPS deficiency group,BH4 response type,and non-reactive type(all P < 0.05),but no significant difference between the BH4 reaction type and the non-reactive group (P > 0.05).Conclusions Through the analysis of the different types of HPA metabolic profiles,it can help to master the incidence and characteristics in the region,within a certain concentration range of blood Phe,the phenylacetic acid,phenyllactic acid,phenylpyruvic acid should not be tested by GC-MS alone.Uterine erythropoietin analysis of BH4D classification and identification of BH4 reaction,non-reactive PKU have a supporting role,so master the metabolic index of various types of concentration and relevance of HPA,it can provide basis for early diagnosis,accurate treatment and follow-up.
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Since 1981,neonatal screening of hyperphenylalaninemia(HPA) has been carrying on in China.The newborns with phenylketonuria(PKU) have been good growthing and developing.Some of them already take part in the marriage period.The fetal brain developmental disorders and various teratogenesis could be leaded if the pregnant women with PKU have high blood concentration of phenylalaninine,namely,maternal PKU syndrome would happen.Now,the international latest progress,including mechanism,prevention,tetrahydrobiopterin support treatment of maternal PKU and the comprehensive management for adult female patients with PKU were summarized,and would like to provide some references for preventing the occurrence of maternal PKU syndrome.
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Tetrahydrobiopterin(BH4) deficiency is a rare type of hyperphenylalaninemia and usually leads to a progressive neurologic deterioration despite early dietary control of blood phenylalanine concentration. We experienced two cases of BH4 deficiency in brother and sister, confirmed by biochemical study of blood and urine. They had suffered from a progressive neurologic illness such as mental retardation, severe hypotonia, seizure, and athetotic movements started at 3 months of their age. Blood amino-acid analysis showed mild hyperphenylalaninemia with elevated urinary neopterin, and reduced urinary biopterin. Their neurologic deteriorations were dramatically improved after replacement of BH4 and dopamine agonist.
Assuntos
Humanos , Biopterinas , Agonistas de Dopamina , Deficiência Intelectual , Hipotonia Muscular , Neopterina , Fenilalanina , Fenilcetonúrias , Convulsões , IrmãosRESUMO
Objective To explore clinical characteristics of phenylalanine hydroxylase(PAH) deficiency in differential diagnosis among hyperphenylalaninemia(HPA) patients and compare the responses to diet treatment in HPA patients.Methods Tetrahydrobiopterin(BH4,20 mg/kg) loading test or combined phenylalanine(Phe,100 mg/kg) and BH4 loading test was carried out among 44 HPA patients.The urine pterine profile analysis and dihydropteridine reductase(DHPR) activity in dry blood filter spot were analyzed simultaneously.Electroencephalogram(EEG) and average full scale development quotient(DQ) were performed in all patients.PAH deficiency patients were given low Phe diet treatment to decrease Phe level for 120-360 ?mol/L and followed up their Phe tolerance.Results Twelve BH4 responsive PAH deficiency patients were diagnosed who were 7 males and 5 females,mean age was 7.8 months.Their metabolic phenotype was moderate or mild HPA.Diet control could decrease Phe level among BH4 deficiency patients but not prevent their neural damage and their EEG abnormal rate was higher.BH4 responsive patients had higher DQ than others and their Phe tolerance increased during diet treatment.Conclusions BH4 responsive PAH deficiency patients can obtain better purpose with diet recipe.The differential diagnosis for BH4 deficiency shall be carried out in all patients with HPA as soon as possible.