RESUMEN
BACKGROUND: Lipoprotein lipase (LPL) deficiency is a monogenic lipid metabolism disorder biochemically characterized by hypertriglyceridemia (HTG) inherited in an autosomal recessive manner. Neonatal onset LPL deficiency is rare. The purpose of this study was to clarify the clinical features of neonatal LPL deficiency and to analyze the genetic characteristics of LPL gene. METHODS: In order to reach a definite molecular diagnose, metabolic diseases-related genes were sequenced through gene capture and next generation sequencing. Meanwhile, the clinical characteristics and follow-up results of the two newborns were collected and analyzed. RESULTS: Three different mutations in the LPL gene were identified in the two newborns including a novel compound heterozygous mutation (c.347G > C and c.472 T > G) and a reported homozygous mutation (c.836 T > G) was identified. Interestingly, both the two neonatal onset LPL deficiency patients presented with suffered recurrent infection in the hyperlipidemia stage, which was not usually found in childhood or adulthood onset LPL deficiency patients. CONCLUSION: The two novel mutaitons, c.347G > C and c.472 T > G, identified in this study were novel, which expanded the LPL gene mutation spectrum. In addition, suffered recurrent infection in the hyperlipidemia stage implied a certain correlation between immune deficiency and lipid metabolism abnormality. This observation further supplemented and expanded the clinical manifestations of LPL deficiency.
Asunto(s)
Hiperlipoproteinemia Tipo I , Hipertrigliceridemia , Lipoproteína Lipasa , Homocigoto , Humanos , Hiperlipoproteinemia Tipo I/diagnóstico , Hiperlipoproteinemia Tipo I/genética , Hipertrigliceridemia/genética , Recién Nacido , Lipoproteína Lipasa/genética , MutaciónRESUMEN
OBJECTIVE: To investigate the relationship of bilirubin/albumin (B/A) ratio and acidosis with abnormal brainstem auditory evoked potentials (BAEPs) in neonates with severe hyperbilirubinemia and its clinical significance. METHODS: A total of 967 neonates with severe hyperbilirubinemia between November 2008 and October 2009 were enrolled in the study. They were divided into two groups according to their BAEPs: normal BAEP group (n=799) and abnormal BAEP group (n=168). Univariate analysis and age-stratified Chi-square test were used to determine the relationship of B/A ratio and acidosis with BAEP. RESULTS: The univariate analysis showed that the abnormal BAEP group had significantly lower pH and base excess values and a significantly higher B/A ratio compared with the normal BAEP group (P<0.05). The age-stratified Chi-square test showed that neonates with acidosis or with a B/A ratio greater than 1.0 had a significantly higher incidence of abnormal BAEPs than those without acidosis or with a B/A ratio less than 1.0 in any age (days) group of neonates with severe hyperbilirubinemia (P<0.05). CONCLUSIONS: High B/A ratio and acidosis are the risk factors for abnormal BAEPs in neonates with severe hyperbilirubinemia, which is the case for those in any age group. In order to reduce the incidence of hearing loss in any age group of neonates with severe hyperbilirubinemia, we should correct the acidosis and lower the B/A ratio as soon as possible.
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Acidosis/fisiopatología , Bilirrubina/sangre , Potenciales Evocados Auditivos del Tronco Encefálico , Hiperbilirrubinemia/fisiopatología , Albúmina Sérica/análisis , Humanos , Hiperbilirrubinemia/sangre , Recién NacidoRESUMEN
Background and objective: Neonatal jaundice is a common clinical disease in neonates. Pathologic jaundice is more harmful to neonates. There are a few studies on the biomarkers of pathologic jaundice and the correlation between gut microbiota and clinical indices. Therefore, we aimed to reveal the characteristics of gut microbiota in pathologic jaundice, provide potential biomarkers for the diagnosis of pathologic jaundice, and find the correlation between gut microbiota and clinical indices. Methods: Fourteen neonates with physiologic jaundice were recruited into a control group (Group A). Additionally, 14 neonates with pathologic jaundice were recruited into a case group (Group B). The microbial communities were analyzed using 16S rDNA sequencing. LEfSe and the differences in the relative abundance of gut microbiota were used to identify different bacteria among the two groups. The ROC curve was used to assess effective biomarkers for pathologic jaundice. Spearman's rank-sum correlation coefficient was used to evaluate the correlation between gut microbiota and clinical indices. Results: There were no differences in the total richness or diversity of gut microbiota between the two groups. At the phylum and genus levels, compared with the control group, Bacteroidetes (p = 0.002) and Braydrhizobium (p = 0.01) were significantly higher, while Actinobacteria (p = 0.003) and Bidfldobacterium (p = 0.016) were significantly lower in the case group. Bacteroidetes were valuable in differentiating pathologic jaundice from physiologic jaundice by the ROC curve, and the area under the ROC curve (AUC) value was 0.839 [95%CI (0.648-0.995)]. In the case group, Bacteroidetes were negatively associated with total bilirubin (TBIL) (p < 0.05). In the control group, Bacteroidetes were positively associated with TBIL (p < 0.05). Conclusion: Bacteroidetes could be used as biomarkers to identify pathologic jaundice and Bacteroidetes are positively associated with bilirubin levels.
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OBJECTIVE: Multiple genetic and environmental factors contribute to the onset of many human diseases, such as neonatal hyperbilirubinemia. OATP 1B1 is an important polymorphism gene which transmembrane transports unconjugated bilirubin(UCB). Genetic polymorphisms that affect the functionality of the protein may potentially lead to altered transport characteristics. The T521C/A388G polymorphism of this gene has been reported to considerably reduce the transporting property of drugs like pravastatin, and may be involved in the membrane translocation of bilirubin. Some studies have shown that OATP 1B1 mediates bilirubin uptake from blood into the liver, and the OATP 1B1 polymorphism is a likely mechanism explaining the differences of bilirubin level in peripheral blood. The aim of this study was to evaluate the relationship between OATP 1B1 polymorphisms and neonatal hyperbilirubinemia. METHODS: A total of 220 newborn infants with hyperbilirubinemia were recruited from Hunan Children Hospital from November 2008 to December 2009 according to the diagnostic criteria. Age and sex matched control subjects comprised of 200 unrelated, hyperbilirubinemia-free newborns. Biochemical and clinical data were collected from the case history. One ml venous blood samples in EDTA vials were taken from each subject and DNA was isolated from peripheral leukocytes by standard methods, preserved in 4°C. 1 - 2 ml venous blood samples were also taken for detecting the serum total bilirubin and direct bilirubin level by chemical oxidation method. OATP 1B1 T521C/A388G polymorphisms were determined using polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) method. Allele and genotype frequencies were compared between patients and control. The gene polymorphism and risk of disease were also analyzed. Serum total bilirubin, conjugated bilirubin and unconjugated bilirubin levels were compared between different OATP 1B1 T521C/A388G genotypes. RESULTS: Allele frequencies in patients and control population were in Hardy-Weinberg equilibrium (P > 0.05). Allele and genotype frequencies of the OATP 1B1 T521C polymorphism in patients were significantly different from the controls. The OATP 1B1 521C allele frequency was only 8.2% in patients, while reached 14.0% in the control group which was very close to the frequency of common Chinese people. However, the proportion of wild type genotypes was significantly higher than those of the controls, reached 84.1%. The 521 C allele and genotypes carrying 521 C allele illustrated low risk for neonatal hyperbilirubinemia (OR = 0.530, 95%CI = 0.328 - 0.857; OR = 0.541, 95%CI = 0.344 - 0.851). However, the frequencies of alleles and genotypes of SLCO1B1 A388G did not differ significantly from those of the controls, and this polymorphism did not influence susceptibility to such disease. Among the three OATP 1B1 A388G genotypes, the level of total serum bilirubin (TSB), direct bilirubin (DB) and unconjugated bilirubin (UCB) were significantly different. Values of TSB, DB and UCB were the highest in wild type subjects, lower in heterozygotes, and the lowest in mutant homozygotes. TSB and UCB in patients with wild type genotypes reached 602.5 µmol/L and 585.0 µmol/L respectively, nearly twice the average value of homozygous patients. While the TSB and UCB in homozygotes were below the average value of all patients, only 351.7 µmol/L and 338.8 µmol/L respectively. CONCLUSIONS: Our findings indicated that OATP 1B1 A388G polymorphism has a notable influence on the serum bilirubin level in neonatal hyperbilirubinemia patients. The OATP 1B1 521T allele may be a potential risk factor of such disease. OATP 1B1 T521C/A388G was an important polymorphism gene which related with neonatal hyperbilirubinemia. Future study should involve other polymorphisms of OATP 1B1, more candidate genes and environmental risk factors. It is also necessary to investigate their association with the severity and prognosis of this disease in order to elucidate the genetic pathogenesis of neonatal hyperbilirubinemia as a complex disease. This study should be repeated in a larger population and different ethnic groups.