Analysis of neonatal hyperphenylalaninemia screening and therapeutic effect in Xuzhou from 2003 to 2015 / 中华围产医学杂志

Objective To investigate the prevalence,clinical classification,treatment and prognosis of neonatal hyperphenylalaninemia(HPA) in Xuzhou area,China.Methods Infants born between July 1,2003 and July 1,2015 in Xuzhou area were investigated.Heel blood samples of neonates were collected at 72 hours after birth,and the concentration of blood phenylalanine(Phe) was determined by fluorescent quantitative method in Xuzhou Maternity and Child Health Care Station Neonatal Disease Screening Center.Differential diagnosis was performed in all 265 cases diagnosed as HPA by urinary pterin analysis and dihydropteridine reductase activity determination.The blood Phe concentration and mental development were followed up regularly in infants with HPA.Mutations of phenylalanine hydroxylase (PAH) gene were analyzed by gene sequencing.The relationship between blood Phe concentration and mental development was analyzed by Bivariate correlation analysis.Results (1) The prevalence of HPA in neonates in Xuzhou was 1/4 635.Among the 265 confirmed HPA cases,260 cases(98.11％) had PAH deficiency,including 90(33.96％) classical phenylketonuria(PKU),84(31.70％) mild PKU and 86(32.45％) mild HPA.The other five patients(1.89％) diagnosed with tetrahydrobiopterin (BH4) deficiency all had 6-pyruvoyl tetrahydropteim synthase(PTPS) deficiency.(2) Among the 265 HPA cases,26 cases refused any treatment,including five cases of PTPS deficiency and 21 cases of PKU.Of the five patients with PTPS deficiency,two died and the other three had normal mental and physical development.Twenty-one PKU patients who refused treatment had mental retardation of various degrees.Among 153 PKU patients who received medical treatment,three died and 12 were lost to follow-up.(3) For 138 PKU patients who received dietary treatment and follow-up,the ages at the last visit were two months to 12 years,116 of them had normal mental development,the remaining 22 patients had mental retardation,and a negative correlation was observed between mental development and the average Phe concentration.(4) Thirty-five patients with PAH deficiency underwent gene sequencing,and 22 kinds of mutations of PAH gene were detected.Conclusions The prevalence of HPA in Xuzhou area is higher than the average national level.With early diagnosis and standard treatment,most of PKU neonates can have normal mental development.Phe level control is an important factor for mental development.

Responsividade à tetrahidrobiopterina em pacientes com deficiência de fenilalanina hidroxilase / Tetrahydrobiopterin responsiveness of patients with phenylalanine hydroxylase deficiency

OBJETIVO: Identificar indivíduos responsivos à tetrahibrobiopterina (BH4) em uma amostra de pacientes brasileiros com hiperfenilalaninemia por deficiência de fenilalanina-hidroxilase (HPA-PAH). MÉTODOS: Estudo intervencional, amostragem por conveniência. Para serem incluídos no estudo, os pacientes deveriam: possuir diagnóstico bioquímico de HPA-PAH; ter idade > 7 anos; estar em tratamento dietético; e apresentar níveis de fenilalanina (Phe) > 6 mg/dL em todas as medidas realizadas no ano anterior à inclusão no estudo. Os níveis de Phe foram determinados por meio de espectrometria de massas in tandem no dia anterior (dia 1) e nos pontos de hora 0, 4 e 8 h (dia 2) e 24 h (dia 3) após ingestão de BH4. Os critérios utilizados para definir responsividade ao BH4 foram: critério 1-redução > 30 por cento de Phe após 8 h da administração de BH4; e critério 2-redução > 30 por cento de Phe após 24 h da administração. RESULTADOS: Dezoito pacientes foram incluídos no estudo (mediana de idade = 14 anos, sexo masculino = 12). Cinco pacientes foram responsivos ao BH4, sendo três (forma clássica: um; forma leve: dois) de acordo com ambos os critérios, e dois (forma clássica: um; forma não definida: um) de acordo com o critério 2. Os níveis de Phe plasmáticos do dia 1 não demonstraram variação nos pontos de hora (p = 0,523). Entretanto, quando comparamos os níveis de Phe nos pontos de hora dos dias 1 e 2, encontramos uma variação significativa (p = 0,006). A análise da associação genótipo-fenótipo confirmou o caráter multifatorial da responsividade ao BH4. CONCLUSÃO: Os nossos achados estão de acordo com a literatura e indicam que um número relevante de pacientes brasileiros com HPA-PAH é responsivo à BH4.

OBJECTIVE: To identify patients responsive to tetrahydrobiopterin (BH4) in a sample of Brazilians with hyperphenylalaninemia due to phenylalanine hydroxylase deficiency (HPA-PAH). METHODS: Interventional study, convenience sampling. The inclusion criteria were: diagnosis of HPA-PAH; age > 7 years; phenylalanine-restricted diet and phenylalanine (Phe) levels > 6 mg/dL in all blood tests 1 year before inclusion. Blood samples were obtained the day before (day 1) and at 0, 4, 8 (day 2) and 24 h (day 3) after BH4 intake. Phe levels were measured using tandem mass spectrometry. The criteria used to define responsiveness to BH4 were: criterion 1- Phe reduction > 30 percent 8 h after BH4 administration; criterion 2 - Phe reduction > 30 percent 24 h after BH4 administration. RESULTS: Eighteen patients were enrolled (median age, 14 years; 12 boys). Five patients were responsive to BH4, 3 according to both criteria (one classical PKU, two mild PKU); and two according to criterion 2 (one classical PKU; one indefinite PKU type). There were no differences between Phe serum levels on day 1 and at the other time points (p = 0.523). However, Phe levels on days 1 and 2 were significantly different (p = 0.006). The analysis of the phenotype-genotype association confirmed its multifactorial character. CONCLUSION: A relevant number of Brazilian patients with HPA-PAH are responsive to BH4, in agreement with other studies in the literature.

Clinical and biochemical study for the diagnosis, treatment and prenatal diagnosis of tetrahydrobiopterin deficiency due to 6 pyruvoyl tetrahydropterin synthase deficiency / 中华围产医学杂志

G) in PTPS gene were identified in 7 families. The third fetus from two families were not affected by PTPS deficiency.

Role and significance of p38 mitogen-activated protein kinase signal transduction pathway in biopterin induction in rats with endotoxic shock / 中华创伤杂志

Objective To investigate the effect of the inhibitor SB203580 of p38 mitogen-activated protein kinase (MAPK) signal transduction pathway on biopterin (BH 4)/nitric oxide (NO) expression and elucidate the potential mechanism of MAPK in biopterin-mediated NO induction after endotoxic shock. Methods A total of 56 male Wistar rats were randomly divided into normal control group (n=8), endotoxic shock group (n=32) and SB203580 treatment group (n=16). After animals were sacrificed, tissue samples from the liver, the lungs as well as the kidneys were harvested to determine the expressions of guanosine triphosphate cyclohydrolase I (GTP-CHI) and inducible nitric oxide synthase (iNOS) mRNA and observe the changes of BH 4 and NO levels in blood and tissues. Results With endotoxin challenge, GTP-CHI mRNA expression and BH 4 levels were significantly elevated in various tissues and maintained at high levels up to 24 hours. Similarly, the iNOS mRNA expression and NO levels in the tissues significantly increased too, especially in the liver and the lungs. Treatment with SB203580 significantly down-regulated GTP-CHI mRNA expression in the liver, the lungs and the kidneys at 12, 24 and 2-12 hours, respectively (P

THE EFFECT OF BIOPTERIN SYNTHESIS INHIBITOR ON ACUTE LUNG INJURY IN POSTBURN STAPHYLOCOCCUS AUREUS SEPSIS / 解放军医学杂志

To determine the role of biopterin in acute lung injury in scald rats with infection, and to observe the therapeutic effect of GTP-cyclohydrolase I(GTP-CHI) inhibitor on postburn sepsis, 56 male Wistar rats were randomly divided into four groups: normal controls (n=10), scald control group(n=10), postburn sepsis group(n=20) and 2,4-diamino-6-hydroxy-pyrimidine (DAHP) treatment group (n=16). Tissue samples from lungs were collected to determine GTP-CHI and inducible nitric oxide synthase (iNOS) mRNA expression, meanwhile biopterin, nitric oxide (NO), tumor necrosis factor-?(TNF-?) and interferon-? (IFN-?) levels in lungs were also measured. The results showed that after scald injury followed by Staphylococcus aureus challenge, GTP-CHI gene expression and biopterin levels significantly elevated in lungs, so did the values of iNOS mRNA expression and NO induction (P