The Clinical Study Of Fabry Disease In Patients With Hypertrophic Cardiomyopathy

Objective:1.By screening the Anderson fabry patients with enzyme technology and molecular biological methods in patients who have been diagnosed as hypertrophic cardiomyopathy,we investigate the probability of misdiagnosing Anderson fabry disease as hypertrophic cardiomyopathy;2.Analysis of Han population in the clinical characteristics of the disease.3.To find mutations which can lead to Anderson fabry disease;4.To establish a method to diagnose Anderson fabry prelinically at enzyme technology and gene level.Method:1.427 unrelated clinical patients diagnosed as hypertrophic cardiomypathy were chosen for the study. After informed consent, a venous blood sample for the plasma a-galactosidase A activity was obtained. Inaddition,one hundred healthy individuals were examined as normal controls. HCM patients with the same sex activity in the control group, said the average ratio of enzyme activity. Patients with low activity (0% to 30% of the normal control in men, and 0% to 50% in women) underwent genetic study of the GLA gene.2.The primers used for amplication of seven exons of Cardiac GLA gene were from adjacent intronic sequence.Seven exons of Cardiac GLA gene were amplifiedusing amplified using polymerase chain reaction(PCR). The PCR products were examined by means of 1.5% agar-gel eleetrophoresis to assay the quantity and specialty.3.Single strand conformation polymorphism(SSCP) was used to detect possible gene mutations in the PCR products. Different conditions were used to enhance the sensitivity of the method;4.Sequence the seven exons and adjacent intronic sequence of Patients with changed strap for exact mutant point.5.The a-galactosidase enzyme activity of patients with mutation were examined. Their family members were screened for Anderson fabry disease with PCR-SSCP; 6.Analysis the correlation between genotypes and phenotypes.Results:1.We have succeeded in 427 patients and 100 normal subjects of the plasma a-galactosidase A activity was detected. Among them, male patients, a total of five people less than 30% of the activity; female patients,a total of eight people less than 50% of the activity. Of these 13 patients had undergone a genetic analysis revealed that:5 patients carrying the GLA gene mutation and the other 4 patients carry mutations in GLA gene polymorphism. Disease-causing mutation are:A143T,E358del,S238N,G1168A and G1170. The activity detection and genetic analysis, a total of 5 patients were diagnosed as Fabry disease. In which female patients carrying the G1168A mutation in family members and another three cases of Fabry disease gene mutation carriers, respectively, for the patient's mother and sister, but no obvious clinical symptoms. Fabry patients for clinical data analysis found that the disease in patients with kidney disease incidence and family history of kidney disease was significantly higher than that in other patients with left ventricular hypertrophy(P<0.05), and ventricular wall thickness, conduction system abnormalities and family history of no significant difference in myocardial(P>0.05).Conclusions:1. Shandong han population type of patients with cardiac muscle is the incidence of illness, fabry for the 1.2%. clause.2 Patients fabry of kidney disease incidence of and the kidney disease family history clearly higher than other patients. Clause.3Of the room with clinically for the merger of kidney disease and kidney family history of the myocardium fleshy, should be alert to the attention of the illness diagnosed, their fabry.