99mTc was used instead of 131I for detecting thyroid tissue in 40 patients with congenital primary hypothyroidism. It was found that 25 cases(62.5%) of athyroidism, 5 cases (12.5%) of ectopic thyroid gland and 10 cases (25%) of thyroid gland in situ. It is suggested that anatomic abnormality of thyroid gland may be the major cause of congenital primary hypothyroidism.

Child ; Humans ; Infant ; Infant, Newborn ; Neonatal Screening ; methods ; Phenylalanine ; blood ; Phenylketonurias ; diagnosis ; genetics ; prevention & control ; Prognosis

Mucopolysaccharidosis type Ⅱ is a rare single gene inherited disorder. In the earlier studies, more attention was paid to the molecular analysis of the hot spots of the mutations. With the detection of more and more novel mutations,more studies are trying to analyze the effect on splicing of different types of mutations and the genotype-phenotype correlations. This review will introduce the progress on molecular genetics, the gene mutation,analysis of the female patients and the genotype-phenotype correlations. With the study of these progress,it suggested that more attention should be paid to the possibility of gene-pseudogen recombinations, trying to study the effect on splicing from the cDNA level, which will benefit the investigation of the genotype-phenotype correlations.

Application of TMS technology in newborn screening has resulted in major expansion of disorder panel for metabolic diseases in recent years. This automated, multiplex testing methodology detects multiple analytes from single analysis of one blood spot, which leads to detection of 30-35 disorders of amino acids, organic acids, and fatty acids metabolism. The early identification of persons affected with inborn errors of metabolism has led to unexpected discoveries related to the natural history of the disorder or options for therapy. This article summarized (1) the basic principles of this technology and methodology. (2) Current status of application of this methodology in the United States, European countries and in China. (3) The positive impacts on the public health and advances in medical genetics. Finally (4) Challenges, issues and possible solutions. The purpose of this article aimed at introducing new technology and exploring the possibilities of implementing into developing countries where medical genetics is not developed and foreseeing the possible problems and obstacles.

Objective To determine the expression of two neuron developmental associated genes induced by hyperphenylalanine.Methods Primary embryonal rat cerebral cortical neurons were cultured for three day and cells induced by hyperphenylalanine for 12 hours.Real time quantitative RT-PCR was used to determine the influence of hyperphenylalanine on the expression of GAP-43 and Go?1 genes.Results GAP-43 mRNA was upregulated to 2.25 times and Go?1 was downregulated to 3.31 times by hyperphenylalanine.Conlusion Hyperphenylalanine may interfere the normal development of cerebral cortical neurons through influencing the expression of GAP-43 and Go?1 genes.

Objective To explore whether phenylalanine affect Cdc42, Racl, and RhoA expression and disturb dendritic development. To determine the effects of brain-derived neurotrophic factor (BDNF) on this process. Methods Neurons were cultivated up to 3 days and then treated with 0.9 mmol/L phenylalanine or 100 ng/ml BDNF. Dendritic number were determined by morphologic analysis. Cdc42, Racl, and RhoA protein expression were examined by Western blotting analysis. ResultsThe number of dendrites in cultured neurons reduced two days after being treated with phenylalanine,while BDNF could rescue this change(P < 0.01), furthermore, BDNF was found to inhibit phenylalanineinduced down-regulation of Cdc42, Racl, and RhoA protein expression(P < 0.01). Conclusions Our study indicated that the protective effect of BDNF against phenylalanine-induced neuronal injury is probably mediated by expression of Cdc42, Racl,and RhoA. It suggested a potential neuroprotective action of BDNF in prevention and treatment of brain injury in the patients with phenylketonuria.

Dried Blood Spot Testing ; Gaucher Disease ; diagnosis ; Humans

Objectives Inborn errors of metabolism (IEM) has a diverse spectrum and different incidence in different countries, the early diagnosis at presymptomatic stage is imperative to benefic patient from sequelae. Phenylke-tonuria (PKU) / hyperphenylalaninemia (HPA) is the most common metabolism disorder in Shanghai as well as in other regions. The study is to further clarify the incidence of inborn errors of metabolism among newborn in Shanghai. Methods The dried blood spot specimens were collected from near 90 local maternity and children's hospitals or general hospitals in Shanghai. PKU/HPA screening was carried out by fluorometric method. Neonatal screening using tandem mass spectrometry was performed in one of the study centers, Xinhua neonatal screening center. Results A total of 815 160 cases were screened from 2001 - 2007 in Shanghai, the incidence of PKU/HPA was 1 : 12 351. The tetrahydrobiopterin deficiency was 12.9% among hyperphenylalaninemia patients. According to the 116 000 neonatal samples data detected by tandem mass spectrometry, 20 cases were confirmed diagnosis, including 6 kinds diseases, it was PKU/HPA, maple syrup urine disease, methylmalonicacidemia, propionic acidemia, 3-methylcrotonyl-CoA carboxylase defection, and short chain aeyl-CoA dehydrogenase deficiency. Conclusions The pilot study shown that inborn errors of metabolism neonatal screen-ing using tandem mass was 1 : 5 800 in Shanghai, PKU/HPA was the most common disease. It is expected that the expansion of newborn screening using tandem mass spectrometry could be further considered and further improving inborn errors of metabolism preventive services in Shanghai.

Biopterin ; analogs & derivatives ; deficiency ; genetics ; Child ; Consensus ; Diagnosis, Differential ; Humans ; Infant ; Infant, Newborn ; Neonatal Screening ; methods ; Phenylalanine ; blood ; Phenylalanine Hydroxylase ; deficiency ; genetics ; Phenylketonurias ; classification ; diagnosis ; therapy ; Practice Guidelines as Topic ; Severity of Illness Index ; Tyrosine ; blood

Objective Establish a method for measuring the activities of Galactocerebrosidase (GALC), α-Glucosidase(GAA), α-Galactosidase (GLA) and α-L-Iduronidase (IDUA) in dried blood spots specimen by tandem mass spectrometry ( MS/MS ).Methods A total of 2175 dried blood spot samples forinborn errors of metabolism in neonatalscreening center of Shanghai Xinhua hospital were collected in July and November, 2013.And twenty dried blood spot samples from patients withlysosomalstorage disorders( LSDs) of Shanghai Xin Hua Hospital were collected from September 2012 to January 2014.The extraction of DBS was incubated with enzyme substrates and internal standards.After liquid-liquid and solid-phase extraction, the extraction solution was dried under nitrogen and reconstituted.Then enzyme reaction products and internal standards were analyzed by MS/MS.Linearity, precision, accuracy and the limit of detection were evaluated.2175 dried blood spot samples were detected to establish the normal reference range for the activities of four enzymes according to 0.5th to 99.5th percentiles.20 specimens from patients withLSDs were detected to verify the reference range inclinical judgment.Results The intraassay and interassay precisions ranged from 1.7%to 11.8%, and the intraassay and interassay accuracies ranged from 85%to 115%.The linear coefficients for measured concentration of enzyme products/internal standards and theoretical concentration were 0.997-0.999.The limits of detection forGALC, GAA, GLA and GLA were 0.03 μmol/(L· h), 0.09 μmol/(L· h), 0.12 μmol/(L· h) and 0.16 μmol/(L· h) .The normal reference values for GALC, GAA, GLA and GLAwere 0.51-8.51μmol( L· h) ,1.99-22.22μmol/( L· h),1.68-41.59 μmol/(L· h) and 2.36-19.21 μmol/(L· h).The enzymes of 20 patients with LSDs were remarkably decreased compared to the normal range.The Krabbe, Pompe, Fabry, MPSⅠpatients can be effectively detected by this MS/MS method.Conclusions A MS/MS method for measuring GALC, GAA, GLA and IDUA enzyme activities in DBShas been established.