Terminal stage cardiac findings in patients with cardiac Fabry disease: an electrocardiographic, echocardiographic, and autopsy study.

OBJECTIVES: Fabry disease is caused by deficiency of alpha-galactosidase A, and typically causes multi-organ dysfunction. Patients with manifestations limited to the heart, mainly left ventricular hypertrophy (LVH), have been reported as a disease variation. We have reported a 3% prevalence of this cardiac variant in men with LVH, which we designated 'cardiac Fabry disease'. The purposes of this study were to evaluate the terminal stage cardiac manifestations and autopsy findings in patients with cardiac Fabry disease. METHODS: We examined seven terminal stage patients with cardiac Fabry disease. During hospitalization, standard 12-lead electrocardiograms, Holter electrocardiograms, and echocardiograms were obtained. Autopsies were performed and macroscopic along with microscopic findings were evaluated. RESULTS: Six patients died of heart failure and one of ventricular fibrillation. Electrocardiograms revealed the presence of conduction abnormalities and nonsustained ventricular tachycardia. Echocardiograms and autopsy findings revealed LVH in all patients. Localized basal posterior wall thinning of the left ventricle was detected in the six patients who died of heart failure. All patients had severe left ventricular dysfunction. Histologically, myocardial cells, but not cardiac vascular endothelial cells, showed glycosphingolipid accumulation. No accumulation was observed in other organs or in systemic vascular endothelial cells. CONCLUSIONS: Severe left ventricular dysfunction with associated conduction disturbances and ventricular arrhythmias occur in patients with terminal stage cardiac Fabry disease. Furthermore, LVH is present and associated with thinning of the base of the left ventricular posterior wall. In contrast to typical Fabry disease, accumulation of glycosphingolipids was observed in myocardial cells but not in other organs.

Effects of neonatally-administered 17beta-estradiol on induction of mammary carcinomas by 7, 12-dimethylbenz[a]anthracene in female rats.

Various doses of 17beta-estradiol (E2) were administered subcutaneously to inbred female Sprague-Dawley (SD) rats once at birth. At 50 days after birth, rats in all the groups were given 10 mg of 7, 12-dimethylbenz[a]anthracene (DMBA). In the 1000 microg group, the incidence and number of mammary carcinomas were markedly low, while in the 10 microg group, a large number of mammary carcinomas was noted. Corpora lutea were observed in all rats in the control, 0.1, 1, 10 and 100 microg groups at 50 days old; however, no corpora lutea were observed in any rat in the 1000 mg group at age 50 days and at sacrifice. Observation of the whole-mount specimens showed a low number of terminal end buds (TEBs) in the 1000 microg group and a high number in the 10 microg group. It is suggested that neonatal administration of E2 affects the gonadotropin-secreting system, resulting in a decrease of progesterone, which is thought to influence the progression of mammary carcinomas induced by DMBA. Moreover, neonatal administration of E2 directly affects the mammary glands, and it is suggested that E2 may promote differentiation of TEBs resulting in inhibitory effects on the initiation of mammary carcinomas.

[End-stage cardiac manifestations and autopsy findings in patients with cardiac fabry disease].

BACKGROUND: Fabry disease is an X-linked recessive disorder resulting from a deficiency of alpha-galactosidase A with multi-organ dysfunction. Patients with manifestations limited to the heart have been reported recently as a disease variant. We have previously reported a 3% prevalence of this cardiac variant in men with left ventricular hypertrophy, which we designated cardiac Fabry disease. The purposes of the current study were to evaluate the end-stage cardiac manifestations and autopsy findings in patients with cardiac Fabry disease. METHODS AND RESULTS: We evaluated five autopsied male patients with cardiac Fabry disease. One died of ventricular fibrillation and four of heart failure. Electrocardiograms obtained at hospitalization revealed the presence of conduction abnormalities and nonsustained ventricular tachycardia. Echocardiograms and autopsy findings showed the presence of left ventricular hypertrophy in all patients. Localized thinning of the basal posterior wall of the left ventricle was detected in four patients who died of heart failure. All patients had severe left ventricular dysfunction. Histologically, myocardial cells showed glycosphingolipid accumulation in all of the patients but no accumulation was observed in other organs or in systemic vascular endothelial cells. CONCLUSIONS: Severe left ventricular dysfunction, conduction disturbances and ventricular arrhythmias occur in end-stage cardiac Fabry patients. Furthermore, left ventricular hypertrophy commonly associated with thinning of the base of the left ventricular posterior wall is present. The accumulation of glycosphingolipids can be observed in myocardial cells but not in other organs.