Analysis Of Regional Characteristics And Death Cases Of Intrahepatic Cholestasis In Infants Caused By Citrin Defects

Part I Different egional distribution of SLC25A13mutations in Chinese patients with neonatal intrahepatic cholestasisAIM To investigate the differences in the mutation spectra of the SLC25A13gene mutations from specific regions of China.METHODS Genetic analyses of SLC25A13mutations were performed in535patients with neonatal intrahepatic cholestasis from our center over eight years. Unrelated infants with at least one mutant allele were enrolled to calculate the proportion of SLC25A13mutations in different regions of China. The boundary between northern and southern China was drawn at the historical border of the Yangtze River.RESULTS A total of63unrelated patients （～11%of cases with intrahepatic cholestasis） from16provinces or municipalities in China had mutations in the SLC25A13gene, of these16（25%） were homozygotes,28（44%） were compound heterozygotes and19（30%） were heterozygotes. In addition to four well described common mutations （c.851₈54del, c.1638₁660dup23, c.615+5G>A and c.1750+72₁751-4dup17insNM₁38459.3:2667also known as IVS16ins3kb）,13other mutation types were identified, including three novel mutations:c.985₉86insT, c.287T>C and c.1349A>G. According to the geographical division criteria,60mutant alleles were identified in patients from the southern areas of China,43alleles were identified in patients from the border, and4alleles were identified in patients from the northern areas of China. The proportion of four common mutations was higher in south region （56/60,93%） than that in the border region （34/43,79%, X2=4.621, P-0.032） and the northern region （2/4,50%, X2=8.288, P=0.041）.CONCLUSION The SLC25A13mutation spectra among the three regions of China were different, providing a basis for the improvement of diagnostic strategies and interpretation of genetic diagnosis. Part II The analysis of8fatal cases with citrin deficiencyObjective Report of fatal cases of patients with neonatal intrahepatic cholestasis caused by citrin deficiency and analysis of factors related to the death.Methods The medical records of all the patients with citrin deficiency were collected from our liver center between Jan.2004to Jan.2012. The clinical manifestations and laboratory data of8fatal cases were reported and a comparative analysis was performed on the manifestations of the death and survival group.Result A total of58patients were diagnosed with citrin deficiency including38males and22females;8patients died,49patients survived, and1patients could not be located. Among the8died patients,4patients confirmed the diagnosis after death for three patients were severe and one was diagnosed as tyrosinemia. Four patients with early diagnosis were given lactose-free and containing medium-chain triglycerides formula; however, infection might contribution to the death.36out of55patients were male and19were female, the mean age was98days（rang40days-1.6year）. The death group had a lower platelets（100.33±17.90vs.407.93±169.74; P=0.003）（10*9/L）, r-GT（129.71±116.11vs.218.99±123.89; P=0.037）（IU/L）, total cholesterol（2.12±1.19vs.3.47±0.97; P=0.012）（mmol/l）,and citrulline（53.59±18.11vs.139.32±80.84）（Um） but higher blood ammonia leave（141.83±45.44vs.100.63±41.67; P=0.03）（umol/L）, tyrosine（195.58±81.28vs.107.81±44.37; P=0.01）（uM） and saw a doctor later（195.63±77.90vs.128.09±97.02days; P=0.006） than survival group. There was no significant difference （P>0.05） in sex, mutation type and coagulation.Conclusion NICCD has a high mortality, which is closely related to visiting age, platelets number, r-GT, total cholesterol, citrulline, blood ammonia and tyrosine. Overview1. The SLC25A13mutation spectra among the three regions of China were different. In the southern region of China, four common mutations is the predominant mutation. The mutations found in patients from the border region exhibited significant variety. Three novel mutations were found.2. NICCD has a high mortality and the infection is the important incentive.3. Visiting age, platelets number, r-GT, total cholesterol, citrulline, blood ammonia and tyrosine were closely related to the mortality.