The Effect Of ApoE Genotype On Clinical Phenotype Of Hypoceruloplasminemia-related Movement Disorder

Objective:To investigate the effect of ApoE genotype on clinical phenotype of hypoceruloplasminemia-related movement disorder(HCMD) without Kayser-Fleischer rings.Methods:From January of 2003 to June of 2007,all patients with movement disorder who enrolled in the out-patient and ward of Department of Neurology of Zhongshan Hospital,Fudan University were screened serum ceruloplasmin(CP) with immuno-nephelometry kit of N antiserum against human CP(Dade Behring,Marburg, Germany) using the described procedure.The patients screened with decreased CP were retested the content of serum CP and,if being confirmed,further investigated total serum copper and 24 hours urine copper with atomic absorption spectrophotometry(Z-8000 Atomic Absorption Spectrophotometer,Hitachi Corporation,Japan).The patients with serum CP≤0.20g/L were further screened through inquiry of medical history,examination of slit lamp corneal microscope,experimental investigation,hepatic ultrasonography,and cranial CT and/or MR scanning.The patients were enrolled as HCMD when they sufficed the following exclusion criteria: Kayser-Fleischer(K-F) ring,hepatic disturbance,renal dysfunction,thyroid disease, parathyroid disease,severe anemia,severe malnutrition,hypoproteinemia,and associated known diseases of basal ganglia.All patients were also excluded possible MD and HA through the consultation discussion of two or more experienced senior neurologists,if necessary,according to both clinical features and experimental data.We identified twenty-eight cases with HCMD and the five WD patients at the same term,which served as WD controls.Twenty-five health volunteers(twenty men and five women) without relative connection and familial history of hereditary diseases were recruited from the students of Shanghai Medical College and served as normal controls.Clinical feature,serum CP,serum copper,urine copper,and Apo E genotypes were investigated in the patients with HCMD and WD.Serum CP and Apo E genotypes were investigated in health control. The results were showed as mean±SEM.Mann-Whitney U test or t test was used as the methods of statistical analysis.The level of significance was assumed to be 5%.Results:Serum CP in HCMD group(0.17±0.023g/L) was lower than that of normal control group(0.291±0.049g/L,p＜0.05).Serum CP in HCMD group was higher than that of WD control group(0.055±0.029g/L,p＜0.05).Serum copper in HCMD group(0.579±0.302μg/L) is higher than that of normal level.Urine copper in HCMD group(297.47±226.44μg/24h) is lower than that of normal level.The frequency of non-ε3/3 genotype of HCMD group(11/24) did not present significant decrease compared with that of normal group(7/25).The frequency of alleleε3 in HCMD group(30/48) did not manifest significant decrease compared with that of normal group(39/50).However,the frequency of alleleε3 in WD group was significantly between WD(4/10) group and normal group.Conelusion:HCMD manifests complicated symptoms and attacks often before 50 years.ApoE genotype does not exert the influence on HCMD clinical phenotype.