Genetic Diseases, Inborn ; economics ; prevention & control ; therapy ; Humans ; Metabolic Diseases ; economics ; prevention & control ; therapy

Objective To explore the effect of the thyroid morphologic change,the initiating treatment time and the thyroid function(serum FT_4,TSH)on mental development in children with congenital hypothyroidism (CH).Methods After diagnosed,52 cases of CH were orally administrated with L-T_4,then their mental and physical development were monitored and thyroid morphologic changes were observed by thyroid imaging(~(99m)TcO_4) and type B ultrasonography.The Bayley test was performed at the age of 10 to 30 months and expressed as mental developmental index(MDI)and psychomotor developmental index(PDI).Analysis was conducted upon treatment timing and thyroid morphologic changes.Results The MDI in those cases with morphologic abnormalities treated within 90 days was significantly lower than that with normal morphology(91?20 vs 105?15,P

Adrenal Hyperplasia, Congenital ; complications ; metabolism ; Body Height ; Growth Disorders ; etiology ; Humans ; Risk Factors ; Steroid 21-Hydroxylase ; metabolism

Objective To investigate the prevalence of adult osteofluomsis in the endemic fluomsis areas in Tianjin and to provide scientific foundation for endemic fluorosis.Methods Stratified sampling in 55 villages were selected in 3 areas with slight,moderate and severe fluorosis regions in Tianjin from April to June in 2008.Water fluorine were tested and clinical osteofluorosis examinations were conducted to the population aging 16 and above in the villages.Tweenty villages were selected randomly in the slight,moderate and severe fluorosis regions.X-ray osteofluorosis examination were conducted to patients and suspected patients in these 20 villages.Results The geometric mean fluoride content in the water for the 3 areas were 1.35 mg/L,3.44 mg/L,5.49 mg/L,respectively.The prevalence of osteofluorosis were 36.7%(44/120),20.6%(33/160),39.4%(43/109),respectively.The prevalence of osteofluorosis Was increased gradually(r=0.534,P<0.01)and the symptoms and signs of the disease were more serious(H=84.813,P<0.01).The prevalence of X-ray diagnosis Was increased gradually(r=0.990,P<0.01)and signs of the disease were more severe(H=25.169,P<0.01)with an increase in age.There was no statistical significance of prevalence rate of osteofluorosis between males and females,regardless if it Was a clinical diagnosis(X2=0.343,P>0.05)or an X-ray diagnosis(X2=3.532,P>0.05).Conclusions Adult osteofluorosis to a certain extent is still prevalent in the fluorosis areas in Tianjin.Endemic fluorosis is still rampant.Improving water in fulorosis areas should be mandatory.

Very long chain acyl-CoA dehydrogenase deficiency(VLCADD)is a disorder involving the initial step of fatty acid beta-oxidation in the mitochondrial matrix. VLCADD can present at various ages,from the neonatal period to adulthood,with symptoms including hypoglycemia,rhabdomyolysis,skeletal muscle weakness and cardiomyopathy,and poses the greatest risk of complications during intercurrent illness or after prolonged fasting. Early diagnosis,treatment,and surveillance can reduce mortality. The most common diagnostic evaluation methods are plasma acylcarnitine profiles and ACADVL gene molecular testing. Functional testing,including white blood cell or fibroblast enzyme assay,is a useful diagnostic adjunct if molecular sequencing alone is insufficient to deter-mine the diagnosis or uncharacterized mutations are identified. Treatment emphasizes the avoidance of fasting and often includes a specialized diet that is high carbohydrate/low longchain fat which is supplemented by medium chain triglycerides(MCT).very-long chain acyl coenzyme A dehydrogenase

Objective:To investigate the effect of paraformaldehyde fixation on measuring the protein-protein interaction by fluorescence resonance energy transfer(FRET)to resolve the problem of FRET efficiency calculation in excess-movement cells.Methods:The C terminals of TCR ? chain(TRA)and TCR ? chain(TRB)genes,which were ideal for protein-protein interaction research,were fused with ECFP and EYFP gene respectively by fusion PCR and transferred into target cell.A grou Pcells were fixed in paraformaldehyde(0.5%)for 0.5~1h and another left alive,then these cells were subject to ECFP/EYFP FRET calculation with confocal laser scanning microscope.The ECFP/EYFP FRET efficiencies in live and fixed cell were analyzed and compared.Results:There is no significant statistical difference between the ECFP/EYFP FRET efficiencies of live cell and cell fixed with lower paraformaldehyde concentration and shorter incubation time.Conclusion:fixation with low-concentration paraformaldehyde and short-time incubation has no distinct influence on measuring protein-protein interaction,and facilitated the FRET calculation in excess-movement cells.

Fatty acid oxidation disorders(FAOD)include more than 10 kinds of diseases,they all belong to autosomal recessive diseases and are common inherited metabolic diseases. Onset age of the patients with FAOD are from newborn to adult. The clinical manifestations were nonspecific,mainly manifested as liver disease,cardiomyopathy and muscle diseases. Detection of free carnitine and acylcarnitines in blood by tandem mass spectrometry and detection of gene mutations are important methods for diagnosis of such diseases. Tandem mass screening for neonatal screening is helpful for early diagnosis and early treatment of FAOD. Primary carnitine deficiency and multiple acyl-CoA dehydrogenase deficiency can be treated by specific therapeutic drugs with good effect. There are no specific drugs for other diseases,which need symptomatic treatment.

Two clinical phenotypes for citrin deficiency (CD) have been reported. One is adult-onset citrullinemia type II (CTLN2) and another is neonatal intrahepatic cholestasis caused by citrin deficiency (NICCD). A child with CD and who had failure to thrive (FTT) and dyslipidemia as main clinical manifestations is reported here. Both the weight-and length-for-age at 18 months dropped below the 3rd percentile in the corresponding WHO anthropometry percentile charts, while blood biochemical analysis revealed dramatically increased triglyceride and total cholesterol, together with reduced HDL-cholesterol. Inquiries revealed his aversion to rice and fondness for fish since the age of one year, a peculiar habit which could not be corrected. Since the age of two years, the peculiar diet became more obvious, and slightly increased citrulline and threonine levels were detected on blood amino acid analysis. At the age of two years and five months he was suspected to have CD. Since then, he has been fed in accordance with his own food preferences, and FTT improved gradually, with weight-for-age, in particular, recovering beyond the 3rd percentile at three years of age, and dyslipidemia was also ameliorated gradually. SLC25A13 gene analysis revealed a homozygote of 851del4, and CD was thus confirmed. Diet survey at four years and seven months revealed a fondness for high-protein and low-carbohydrate foods, such as seafood, meat, eggs and milk. This child presented with FTT and dyslipidemia as main clinical manifestations and this was a novel CD phenotype different from NICCD and CTLN2.
Body Weight ; Calcium-Binding Proteins ; deficiency ; Cholestasis, Intrahepatic ; etiology ; Citrulline ; blood ; Dyslipidemias ; etiology ; Failure to Thrive ; etiology ; Humans ; Infant ; Lipids ; blood ; Male ; Mitochondrial Membrane Transport Proteins ; genetics ; Mutation ; Organic Anion Transporters ; deficiency ; Phenotype

OBJECTIVETo report the results of clinical characteristics, enzyme activity determination and mutation analysis of GLB1 gene in a Chinese patient with mucopolysaccharidosis (MPS) type IVB (Morquio B disease).

METHODA 14-year-old Chinese boy with MPS type IVB was firstly diagnosed by blood leucocytes galactosamine-6-sulfate sulfatase (GALNS) and β-galactosidase (GLB1) determination, who was characterized by short stature, multiplex skeletal abnormalities, difficulty in walking. PCR-sequencing analysis was applied to detect the mutations in GLB1 of the patient.

RESULTThe patient was characterized by dwarfism, pectus carinatum, kyphosis, normal intelligence, and no neurologic damage of spasms, linguistic capacity and so on. The patient had normal GALNS enzyme activity and very low GLB1 enzyme activity [5.03 nmol/(h·mg) vs. normal value 118 - 413 nmol/(h·mg) ] in leukocytes. A compound heterozygous missense mutations c.442C > T(p.R148C)/c.1454A > G(p.Y485C) in GLB1 gene were detected in this patient. The mutation p.Y485C is a novel variant. With the method of gene analysis of new variant, the mutation p.Y485C was considered to be a pathogenic mutation.

CONCLUSIONThe MPS IVB patient showed severe multiple skeletal deformities, normal intelligence, no neurologic damage and very low GLB1 enzyme activity, who carries compound heterozygous mutations p.R148C/p.Y485C. The mutation p.Y485C in GLB1 gene may be a novel pathologic mutation of MPS type IVB.

Adolescent ; Amino Acid Sequence ; Asian Continental Ancestry Group ; genetics ; Chondroitinsulfatases ; genetics ; metabolism ; DNA Mutational Analysis ; Humans ; Joints ; pathology ; Male ; Molecular Sequence Data ; Mucopolysaccharidosis IV ; enzymology ; genetics ; pathology ; Mutation, Missense ; Pedigree ; Polymerase Chain Reaction ; Radiography ; Spine ; diagnostic imaging ; pathology ; beta-Galactosidase ; genetics ; metabolism