Coronary disease, cardioneuropathy, and conduction system abnormalities in the cardiomyopathy of Friedreich's ataxia.

Abstract

SUMMARY Abnormalities of the heart are a frequent and possibly ubiquitous problem in patients with Friedreich's ataxia, but their pathogenesis is unclear. Postmortem findings are reported from the hearts of three patients with Friedreich's ataxia who died of congestive heart failure and atrial arrhythmias. Particular attention was paid to the following: the large and small coronary arteries, the nerves and ganglia, the conduction system, and the histological and cellular features of the cardiomyopathy. There were pleomorphic nuclei and focal fibrosis and degeneration throughout each heart including the conduction system. There were distinctive abnormalities of both large and small coronary arteries, and focal degeneration of nerves and ganglia. These observations suggest a mosaic concept for the pathogenesis for the cardiomyopathy of Friedreich's ataxia that involves the interplay of molecular faults, cardiomyopathy, cardioneuropathy, and coronary disease.In Friedreich's original description of the heritable ataxia that now bears his name he reported that five of his six cases showed clinical evidence of heart disease.1 Although the existence of such heart disease has been recognised for many years-and despite Friedreich's own experience-it has only recently come to be widely appreciated how often the heart is abnormal in these ataxic individuals.

Preclinical and manifest diabetes mellitus in young patients with friedreich's ataxia: no evidence of immune process behind the islet cell destruction

“…In this respect, it has to be considered that other organs (spinocerebellar centres and cardiac cells) undergo degeneration or destruction of cells in FA. The heart disease has been shown [21] to be due to abnormalities of myocardial cells with hypertrophy, fibrosis and pleo- Fig. 1.…”

“…K= In (t/2) 10% 5% Table 2 ; '2'~ '2o 6' o morphic nuclei, degeneration of neuronal cells in nerves and ganglia and lesions of small and large coronary arteries. A more general molecular disorder has been postulated as a cause of these changes [21]. A link or common factor responsible for cell degeneration in different organs of patients with FA is therefore conceivable.…”

Evaluation of the Cases with Friedreich Ataxia

“…Afferent visual pathways may also be affected. Besides nervous system, degeneration of cardiomyocytes and β cells of pancreas are also reported (6,7). Although symptoms of the disease start between the ages of 5-15, there may be early and late onset cases (5).…”

Management and therapy for cardiomyopathy in Friedreich’s ataxia

“…Pathological samples are available both from autopsy tissue (usually patients dying from heart failure as a result of cardiomyopathy with progressive dilation) and occasionally biopsy samples [49,50]. In autopsies, four-chamber dilation has been observed with microscopic pathology demonstrating cardiac hypertrophy, atrophy and fibrosis.…”