OBJECTIVETo investigate the mutations of SLC22A5 gene in patients with systemic primary carnitine deficiency (CDSP).

METHODSHigh liquid chromatography tandem mass spectrometry (HPLC/MS/MS) was applied to screen congenital genetic metabolic disease and eight patients with CDSP were diagnosed among 77 511 samples. The SLC22A5 gene mutation was detected using massarray technology and sanger sequencing. Using SIFT and PolyPhen-2 to predict the function of protein for novel variations.

RESULTSTotal detection rate of gene mutation is 100% in the eight patients with CDSP. Seven patients had compound heterozygous mutations and one patient had homozygous mutations. Six different mutations were identified, including one nonsense mutation [c.760C>T(p.R254X)] and five missense mutations[c.51C>G(p.F17L), c.250T>A(p.Y84N), c.1195C>T(p.R399W), c.1196G>A(p.R399Q), c.1400C>G(p.S467C)]. The c.250T>A(p.Y84N) was a novel variation, the novel variation was predicted to have affected protein structure and function. The c.760C>T (p.R254X)was the most frequently seen mutation, which was followed by the c.1400C>G(p.S467C).

CONCLUSIONThis study confirmed the diagnosis of eight patients with CDSP on the gene level. Six mutations were found in the SLC22A5 gene, including one novel mutation which expanded the mutational spectrum of the SLC22A5 gene.

Adult ; Amino Acid Sequence ; Base Sequence ; Cardiomyopathies ; diagnosis ; genetics ; metabolism ; Carnitine ; deficiency ; genetics ; metabolism ; DNA Mutational Analysis ; methods ; Female ; Gene Frequency ; Genotype ; Humans ; Hyperammonemia ; diagnosis ; genetics ; metabolism ; Infant, Newborn ; Male ; Muscular Diseases ; diagnosis ; genetics ; metabolism ; Mutation ; Organic Cation Transport Proteins ; genetics ; metabolism ; Reproducibility of Results ; Sensitivity and Specificity ; Sequence Homology, Amino Acid ; Solute Carrier Family 22 Member 5 ; Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization

OBJECTIVETo investigate the predictors that reduced the survival time on HIV positive TB patients during their first year's anti-TB therapy.

METHODSA retrospective study was conducted to review 519 TB/HIV co-infection patients from an Internet based TB surveillance system. We collected information of demography, HIV status, CD4+ lymphocytes count, antiretroviral therapy (ART), sputum smear results of diagnosis and around 2 months' initiation of anti-TB therapy, et al. Wilconxon rank sum test was used to compare the difference of age and CD4+ lymphocytes, count and Cox Uni-variable, and Multi-variable analysis were used to compare the different distribution of rest of risk elements between the groups of death and survival; survival function also has been used to evaluate the top 4 risk elements that have made negative impact on the survival time of HIV positive TB patients during their first year's anti-TB therapy.

RESULTSAmong 519 TB/HIV patients, 84 (16.18%) were dead, 435 (83.82%) survived. Median age (P50 (P25-P75)) in survival was 51.0 (41.0-65.0), while in death was 45.0 (35.0-60.0) (U=-2.68, P=0.007). There was significant difference between survival and death. Median CD4+ lymphocyte count in survival and death (P50 (P25-P75)) were 69.00 (26.00-131.20) and 114.50 (35.00-245.00), respectively, significant difference also has been observed. Based on the Cox analysis, patients with less than 2 months' intensive anti-TB therapy, poor treatment adherence, less than 4 months continue anti-TB therapy and sputum smear positive around 2 months initiation of anti-TB therapy had higher risk of death, the Relative Risk value (RR) were 1 100.40 (95% CI: 105.62-11,470.00), 52.91 (95% CI: 27.42-102.13), 49.43 (95% CI: 6.38-382.81), and 15.83 (95% CI: 2.55-98.40), respectively. Log-rank test results showed that there were significant difference between survival and death groups with anti-TB intensive therapy duration (Log-Rank value was 236.0, P<0.001), adherence (Log-Rank value was 302.9, P<0.001), and sputum smear results around 2 months' anti-TB initiation (Log-Rank value was 7.55, P=0.006).

CONCLUSIONKnown HIV positive, less CD4+ lymphocyte count, not initiation of ART, sputum smear positive, around 2 months' initiation of anti-TB therapy, not enough anti-TB therapy duration of intensive and continue period and poor treatment adherence were the predictors of death of HIV positive TB patients in the first year's anti-TB therapy.

Anti-HIV Agents ; CD4 Lymphocyte Count ; CD4-Positive T-Lymphocytes ; Coinfection ; Factor Analysis, Statistical ; HIV Infections ; Humans ; Life Expectancy ; Retrospective Studies ; Survival Rate ; Tuberculosis

OBJECTIVETo detect potential mutations in six patients with citrullinemia.

METHODSGenomic DNA was extracted from peripheral blood samples from the patients. Mutations of the ASS1, ASL and SLC25A13 genes were screened using microarray genotyping combined with direct sequencing.

RESULTSOne patient was diagnosed with argininosuccinate lyase deficiency, and has carried a homozygous c.1311T>G (p.Y437*) mutation of the ASL gene. The remaining five patients were diagnosed with neonatal intrahepatic cholestasis due to citrin deficiency, and have respectively carried mutations of the SLC25A13 gene including [c.851-854delGTAT+c.851-854delGTAT], [c.851-854delGTAT+IVS6+5G>A], [c.851-854delGTAT+IVS16ins3kb], [c.851-854delGTAT+IVS6-11A>G] and [c.851-854delGTAT+c.1638-1660dup23]. Among these, the c.1311T>G mutation was first identified in the Chinese population, and the IVS6-11A>G mutation was a novel variation which may affect the splicing, as predicted by Human Splicing Finder software.

CONCLUSIONThis study has confirmed the molecular diagnosis of citrullinemia in six patients and expanded the mutational spectrum underlying citrullinemia.

Argininosuccinate Lyase ; genetics ; Argininosuccinate Synthase ; genetics ; Citrullinemia ; genetics ; DNA Mutational Analysis ; Female ; Humans ; Infant ; Infant, Newborn ; Male ; Mitochondrial Membrane Transport Proteins ; genetics ; Mutation

Objective To understand the general feature of patients with Mycobacterium tuberculosis(MTB)and human immunodeficiency virus(HIV)co-infectious(TB/HIV)in Guangxi, from 2007 to 2012. Methods Information regarding individuals that the contributory causes of death were due to MTB infection among HIV as the underlying cause of death from the Vital Registration System,together with bacterium smear or culture results,onset of TB,time that TB was diagnosed and entered an Internet base TB surveillance system was collected and checked. Data including information on time of death,age,occupation,the underlying cause of death among TB patients, bacterium distribution,average age of death,interval from onset to death,percentage of TB/HIV co-infection patients among all the patients etc,were all analysed. Results 203 patients died from HIV associated with TB from the Guangxi Vital Registration System were identified between 2007 and 2012. The average percentage of TB/HIV co-infection cases accounted for 8.24%(ranging from 3.94%in 2007 to 13.27%in 2012)among all the deaths of HIV infection while it accounted for 9.90%(ranging from 2.56%to in 2007 to 26.88%in 2012)among patients with MTB infection in the same period. The average percentage of deaths from TB/HIV co-infection in 2010 and 2012 accounted for 10.66%(ranging from 8.83% to 13.27%) and 22.17%(ranging from 20.60% to 26.88%) among patients died of HIV and TB infection respectively. The male-female ratio was 4.21 for 1,with the average age of death as 44.65 (44.65 ± 15.52)years;median time from TB symptoms onset to diagnosis as 37(mean 94.31,standard deviation 206.07)days,record as(94.31 ± 206.07);median time from diagnosis to death as 46(165.22 ± 282.19)days,54.68%TB/HIV patients died within two months of being diagnosed with TB and the median time from TB symptoms onset to death as 131 (257.68 ± 340.79) days. 16.26% of the TB/HIV cases were bacterium confirmed TB cases. Conclusion Compare to those TB patients without HIV,less bacterium evidence was found in TB/HIV patients. High burden caused by HIV disease was seen if they were co-infected with TB. An increasing proportion of deaths was noticed among patients co-infected with HIV and TB in the last three years,suggesting that the coverage of antiretroviral therapy be scaled up together with the strengthening of the capability on early TB case-finding among people live with HIV.

OBJECTIVE To detect potential mutations of GCDH gene in five patients with glutaric acidemia type I (GA-I). METHODS Genomic DNA was extracted from peripheral blood samples from the patients. The 11 exons and their flanking sequences of the GCDH gene were amplified with PCR and subjected to direct sequencing. RESULTS Four mutations of the GCDH gene were identified among the patients, which included c.532G>A (p.G178R), c.533G>A (p.G178E), c.106_107delAC (p.Q37fs*5) and c.1244-2A>C. Among these, c.1244-2A>C was the most common, while c.106_107delAC was a novel mutation, which was predicted to be pathogenic by MutationTaster software. CONCLUSION The diagnosis of GA-I has been confirmed in all of the five patients. Identification of the novel GCDH mutations has enriched the mutational spectrum of the GCDH gene.

OBJECTIVETo understand the general feature of patients with Mycobacterium tuberculosis (MTB) and human immunodeficiency virus (HIV) co-infectious (TB/HIV) in Guangxi, from 2007 to 2012.

METHODSInformation regarding individuals that the contributory causes of death were due to MTB infection among HIV as the underlying cause of death from the Vital Registration System, together with bacterium smear or culture results, onset of TB, time that TB was diagnosed and entered an Internet base TB surveillance system was collected and checked. Data including information on time of death, age, occupation, the underlying cause of death among TB patients, bacterium distribution, average age of death, interval from onset to death, percentage of TB/HIV co-infection patients among all the patients etc, were all analysed.

RESULTS203 patients died from HIV associated with TB from the Guangxi Vital Registration System were identified between 2007 and 2012. The average percentage of TB/HIV co-infection cases accounted for 8.24% (ranging from 3.94% in 2007 to 13.27% in 2012) among all the deaths of HIV infection while it accounted for 9.90% (ranging from 2.56% to in 2007 to 26.88% in 2012) among patients with MTB infection in the same period. The average percentage of deaths from TB/HIV co-infection in 2010 and 2012 accounted for 10.66% (ranging from 8.83% to 13.27%)and 22.17% (ranging from 20.60% to 26.88%)among patients died of HIV and TB infection respectively. The male-female ratio was 4.21 for 1, with the average age of death as 44.65 (44.65 ± 15.52) years;median time from TB symptoms onset to diagnosis as 37 (mean 94.31, standard deviation 206.07) days, record as (94.31 ± 206.07); median time from diagnosis to death as 46 (165.22 ± 282.19) days, 54.68% TB/HIV patients died within two months of being diagnosed with TB and the median time from TB symptoms onset to death as 131 (257.68 ± 340.79) days. 16.26% of the TB/HIV cases were bacterium confirmed TB cases.

CONCLUSIONCompare to those TB patients without HIV, less bacterium evidence was found in TB/HIV patients. High burden caused by HIV disease was seen if they were co-infected with TB. An increasing proportion of deaths was noticed among patients co-infected with HIV and TB in the last three years, suggesting that the coverage of antiretroviral therapy be scaled up together with the strengthening of the capability on early TB case-finding among people live with HIV.

Adult ; China ; epidemiology ; Coinfection ; mortality ; Female ; HIV Infections ; microbiology ; mortality ; Humans ; Male ; Middle Aged ; Tuberculosis ; mortality ; virology ; Young Adult