Fabry disease--a diagnostic and therapeutic problem.

The authors present a patient with Fabry syndrome that remained undiagnosed for several years. Fabry syndrome is a genetic disease related to changes on the X chromosome. Its complex clinical presentation and diverse symptomatology is caused by deficient activity of lysosomal hydrolase alpha-galactosidase enzyme. Defect in the basic alpha-galactosidase molecule implies genetic change, which can be a predisposing factor for the development of atypical and typical forms of this genetic disease. In the presented case, clinical manifestation and hemizygous symptomatology were the evidence of metabolic and genetic irregularity, typical clinical presentation of Fabry disease. Many authors report generalized vasculopathy as a basic characteristic of Fabry disease and a causative factor of multiorgan changes. Some authors indicate that persons with diagnosed asymmetric hypertrophy of the left ventricle have decreased alpha-galactosidase. Cardiac complications, coronary disease, and acute myocardial ischemia are often present in cases of Fabry disease, frequently causing death in such patients. Characteristic central nervous system symptoms with skin-burning sensation and paresthesia were also present in our case. Cerebrovascular complications were caused by changes on small blood vessels. Clinical signs of renal failure were nonspecific, and the diagnosis was based on extrarenal symptoms. Initial renal manifestations were insignificant as asymptomatic proteinuria and microhematuria, due to which our patient was referred to further examination. The level of alpha-galactosidase was significantly decreased. The severity and progression of this disease depends on the level of alpha-galactosidase enzyme in serum and its catabolic effect. More recent studies have showed that deficient enzyme can be synthetic zed and, accordingly our patient has been successfully enrolled in the replacement therapy program.

Dyslipoproteinemia and coronary disease.

Dyslipoproteinemia is involved in the origin of arteriosclerosis by changing the architecture of the coronary artery wall and therefore represents an important factor in the development of coronary artery disease (CAD). High-density lipoprotein (HDL) and apolipoprotein-A1 (Apo A1) serve as protection against the origin and development of coronary obstructive disease. The aims of this study were to evaluate the relations among the plasma lipids, their fraction Apo A1, HDL, and positive coronary arteriography, and to estimate their importance as markers of the degree of coronary lesions. The study included 101 subjects, 77 men and 24 women, aged 35 to 75 years, mean age = 55.7 years. The subjects were divided into 2 groups: 1 group--CAD with positive coronary arteriography (n = 70), and the other group--CAD with negative coronary arteriography (n = 31). According to the anatomic localization of atherosclerotic lesion, the first group of subjects was divided into 1-vessel (n = 26), 2-vessel (n = 20), and multiple-vessel lesion (n = 24) subgroups. The results show a significant difference in Apo A1 and Apo A1/Apo B (p<0.005) in the 2- and multiple-vessel disease in relation to the control group, while subject significance was not proved for 1-vessel disease. A positive correlation and significance for HDL as well as cholesterol ratio/HDL (p<0.05) was noted for 1- and multiple-vessel disease, while a negative correlation was noted for 2-vessel disease in relation to the control group. This study stressed the diagnostic significance in determining Apo A1 and Apo A1/Apo B1 as better predictors than HDL cholesterol in evaluating coronary lesion severity. Dyslipoproteinemia, namely, the level of lipoproteins of low density, plays an important role in the pathogenesis of arteriosclerosis and the development of CAD.