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

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.

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.

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.

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.

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.

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

Dried Blood Spot Testing ; Gaucher Disease ; diagnosis ; Humans

Objective To analyze gene mutations of a Niemann-Pick disease type C (NPC) proband,and carry out prenatal diagnosis for the family.Methods The coding regions of NPC1 gene in the proband (late-infantile form) and white blood cell (WBC) in peripheral blood of its parents were amplified by polymerase chain reaction and direct DNA sequencing in both directions was performed.The sequencing results were compared with human NPC1 gene sequence (NM_000271) in GenBank,and sequences of mutated exons were determined.Direct sequencing was used on 50 normal Chinese individuals' DNA samples (control) to exclude mutation's single nucleotide polymorphism (SNP).An inter-species alignment of homologous NPC1 proteins was performed using ClustalX 1.81 software.During the second pregnancy of the proband's mother,the amniotic fluid was obtained at 18 weeks of gestation and the amniocytes were cultured for gene mutation analysis.Neonate's DNA of WBC in peripheral blood was also extracted for NPC1 gene analysis.Results Mutation analysis of NPC1 gene revealed two novel heterozygous mutations (c.2284-2287 delCTCT and p.V959G) in the proband,which originated from her father and mother,respectively.These two mutations were absent in the control,suggesting that these mutations were not SNP.While comparing with the amino acid in NPC1 protein of human,mouse,rat,rabbit,cat and pig,it revealed that p.V959 belonged to a conservative amino acid region and the missense mutation of p.V959G may perturb the function of NPC protein.Neither mutation was found in DNA from amniotic fluid or from the cultivated amniocytes in the second pregnancy,suggesting a normal fetus.c.2284-2287 delCTCT and p.V959G mutation were not found in NPC1 gene analysis of WBC in peripheral blood of the neonate,which was consistent with the prenatal diagnosis.Conclusions PCR-direct sequencing could be used as genetic diagnosis for NPC proband and prenatal diagnosis for its family.The mutation p.V959G may be correlated to late infantile form of NPC.