Clinical and variation analysis of three Chinese families affected with glutaric acidemia type 1 / 中华医学遗传学杂志

OBJECTIVE@#To detect potential variation in glutaryl-CoA dehydrogenase (GCDH) gene among three Chinese families affected with glutaric acidemia type Ⅰ(GA-1) and correlate the genotypes with phenotypes.@*METHODS@#Genomic DNA was extracted from peripheral blood samples derived from three patients with GA-1 and their family members. The coding regions of the GCDH gene were amplified with PCR and subjected to Sanger sequencing.@*RESULTS@#The clinical manifestation of the patients varied from macrocephaly to severe encephalopathy, with notable phenotypic difference between siblings carrying the same variation. In pedigrees 1 and 2, the probands have carried compound heterozygous variations c.1133C>T(p.Ala378Val) and c.1244-2A>C, which were derived their fathers and mothers, respectively. In pedigree 3, the proband has carried compound heterozygous variation c.339delT (p.Tyr113) and c.406G>T (p.Gly136Cys). Among these, variations c.339delT and c.1133C>T were verified as novel by retrieval of dsSNP, HGMD and 1000 genome database. Bioinformatic analysis suggested that above variations can affect protein function and are probably pathogenic.@*CONCLUSION@#Above discovery has expanded the mutation spectrum of the GCDH gene. No correlation was found between the clinical phenotype and genotype of GA-1 patients.

The value of combination of the mortality in emergency department sepsis score and blood lactate level in the risk stratification of severe sepsis in the emergency department / 中华危重病急救医学

Objective To evaluate the combination of the mortality in emergency department sepsis (MEDS) score with blood lactate level in the risk stratification of patients with severe sepsis in the emergency department (ED).Methods 665 adult patients with severe sepsis admitted from May 2011 to December 2012 in ED were found to be eligible for the study.MEDS score,acute physiology and chronic health evaluation Ⅱ (APACHE Ⅱ) score,and arterial blood lactate was determined,and the outcomes in 28 days were recorded.Logistic regression analysis was used to evaluate the relationship between each predictive factor score and prognosis.Each predictive factor was compared with the areas under the receiver operating characteristics (ROC) curve (AUC).Results The mortality in 28 days was 34.6％ in 665 patients.The mortality in group of MEDS score 12-27 was significantly higher than that group of MEDS score＜12 [51.0％ (156/306) vs.20.6％ (74/155),x2=28.414,P=0.000].In the meantime,APACHE Ⅱ score and blood lactate level were also significantly higher in group of MEDS score 12-27 than those in group with MEDS score＜12 [APACHE Ⅱ score:26.4 ± 10.6 vs.21.7 ± 8.1,t=-3.555,P=0.002; lactate (mmol/L):4.9 (2.3,9.9)vs.3.9 (1.5,8.9),Z=-2.352,P=0.023].Kaplan-Meier survival analysis showed significantdifference in the two groups (the Log Rank test 36.71,P ＜0.01).The levels of 3 predictive factors were predominantly higher in non-survivors than survivors [MEDS score:14.1 ± 6.7 vs.8.2 ± 4.5,t=-6.929,P=0.000; APACHE Ⅱ score:28.1 ±7.1 vs.22.2± 11.3,t=-6.472,P=0.000; lactate (mmol/L):5.4 (2.9,11.0) vs.3.8 (1.2,9.1),t=-6.472,P=0.004].The AUCs were 0.813,0.706 and 0.727 for MEDS score,APACHE Ⅱ score and blood lactate respectively.The predictive ability for 28-day mortality of MEDS score was better than blood lactate (P=0.008) and APACHE Ⅱ score (P=0.005).The AUC of MEDS score combined with lactate was 0.865,and 28-day mortality prediction was better than MEDS score (AUC 0.865 vs.0.813,P＜0.001).The sensitivity (83.1％),specificity (93.2％),positive prediction value (PPV,62.4％),and negative prediction value (NPV,92.1％) for MEDS score combined with lactate were highest among all predictors.Conclusion MEDS score combined with lactate is a good risk stratification tool for emergency patients with severe sepsis,and its prognostic capability is better than either MEDS score,APACHE Ⅱ score or blood lactate.

Clinical investigation and genetic analysis of a Chinese family with glutaric acidemia type I / 中华医学遗传学杂志

<p><b>OBJECTIVE</b>To review the clinical features of a families affected with glutaric acidemia type I (GA-1) and screen potential mutations in glutaryl-CoA dehydrogenase (GCDH) gene.</p><p><b>METHODS</b>Clinical data of the patients and their family members was analyzed. Genomic DNA was extracted from peripheral blood samples. The 11 exons and flanking sequences of the GCDH gene were amplified with PCR and subjected to direct DNA sequencing.</p><p><b>RESULTS</b>Two patients have manifested macrocephaly. Imaging analysis revealed arachnoid cyst and subdural effusion. The elder sister had encephalopathy crisis. The younger sister had significantly raised glutaric acid, whilst the elder sister was normal during the non-acute phase. Genetic analysis has revealed a homozygous c.1244-2A> C mutation of the GCDH gene in both patients.</p><p><b>CONCLUSION</b>The clinical features and mutation of the GCDH gene have been delineated in a Chinese family affected with GA-1. The c.1244-2A> C mutation may be particularly common in the Chinese population.</p>