Preliminary Study On The Diagnosis Process For Wilson's Disease In Chinese Children And Adults

OBJECTIVE: The purpose of this paper is to analyze the application of various indicators in the Leipzig scoring system in different age groups in China,and to explore the diagnostic procedures suitable for Chinese children and adults WD,so as to improve the early diagnosis rate of WD.Research methods: Collecting clinical data of 54 cases of WD and the control group(non-WD)in the Third People's Hospital of Shenzhen January 2011 to December 2018.The collected cases were grouped according to age,respectively group A1(0-6 years old,WD),A2group(0-6 years old,non-WD),B1 group(6-18 years old,WD),B2 group(6-18 years old,non-WD)and C group(>18 years old,WD).The following statistical analysis was performed on the data of each group of WD patients:(1)The spearman rank correlation analysis between scores of various test detections(ceruloplasmin,24-hour urinary copper excretion,K-F rings)and age groups,to identify the index-sensitive detection of various ages;(2)The Leipzig score as the diagnostic gold standard,then the sensitivity,specificity,positive predictive value and negative predictive value of the combined detection method of each age group were calculated;(3)Calculate the area under the curve(Area Under Curve,AUC)and P value according to the sensitivity and specificity of each combined detection method,and evaluate the diagnostic efficiency of the combined detection method;(4)Kappa consistency test was used to test the consistency of diagnosis results between the combined detection and Leipzig score;(5)The difference between the diagnostic positive rate of the combined detection method and the positive rate of Leipzig score was analyzed by chi-square test.Finally,based on the above statistical analysis results,a simple diagnosis and treatment process is designed for WD patients of different ages.RESULTS:(1)The positive detection rate of ceruloplasmin(CER)and 24-hour urinary copper excretion was higher in all age groups(100%,100%,100% and 93.74%,85.71%,100%,respectively).There is no significant correlation between the scores of these two indicatorsand age(P = 0.301,0.512,respectively),which proves that both CER and 24-hour urinary copper are suitable for the diagnosis of WD in all ages.The positive detection rate of K-F rings(Kyner-Fleischer rings)increased with age(0%,55.56% and 100%,respectively),and the scores were significantly positively correlated with age(P<0.001,correlation coefficient rs = 0.792),which proves that K-F rings is suitable for the diagnosis of WD older than 6 years old.(2)96.3%(26/27)patients can rely on genetic testing to confirm WD,suggesting that ATP7 B gene detection has a greater diagnostic value.The diagnostic rates of the Leipzig scoring system without gene diagnosis in all ages were 38.1%(0-6 years old),58.3%(6-18 years old),and 90%(>18 years old),suggesting that most children rely on genetic testing to diagnosis WD.Especially asymptomatic children aged 0-6 years.(3)For the screening of suspicious WD patients aged 0-6 years,it is recommended to use the combined detection method include CER and 24-hour urinary copper excretion,the sensitivity is 93.75%,the specificity is 100%,the positive predictive value is 100%,the negative predicted value is 96.15%;AUC is 0.969,P<0.001,suggesting that the combined detection has a high diagnostic efficiency;the combined detection has a strong consistency with the Leipzig scoring system(P<0.05,Kappa coefficient is 0.948);the positive rate of the combined detection diagnosis(93.75%)was compared with the positive rate of the Leipzig scoring system(100%),P>0.05,the difference was not statistically significant.For the screening of suspicious WD patients aged 6-18 years,it is recommended to use combined detection method include CER,24-hour urinary copper excretion,and K-F rings.The sensitivity is 85.71%,the specificity is 100%,and the positive predictive value is 100.%,the negative predictive value is 83.33%;AUC is 0.93,P=0.015,suggesting that combined detection method have high diagnostic efficacy;the combined detection method have significant consistency with the Leipzig score(P<0.05,Kappa coefficient is 0.83);the positive rate of the combined detection and diagnosis(85.71%)was compared with the positive rate of Leipzig score(100%),P>0.05,the difference was not statistically significant.Conclusions:(1)Patients aged 0-6 years diagnosis WD need to rely on ATP7 B gene test.the combined detection method of CER and 24-hour urinary copper excretion is suitable for screeningsuspicious WD in this age group.(2)Among patients aged 6-18 years,half need to rely on the ATP7 B gene test to confirm the diagnosis,half can be diagnosed by the combined detection of CER,24-hour urinary copper excretion,and KF rings.And this combined detection is suitable for screening suspicious WD in this age group.(3)Patients older than 18 years old can be diagnosed according to typical clinical symptoms,copper metabolism indicators,etc.,independent of ATP7 B gene test.