CARDIAC AMYLOIDOSIS - A REVIEW AND REPORT OF A NEW TRANSTHYRETIN (PREALBUMIN) VARIANT

Cardiac amyloidosis is caused by amyloid deposits derived from differe nt human plasma proteins. It can lead to cardiac conduction disturbanc es, restrictive cardiomyopathy, and low output heart failure. The hear t is variably involved during the development of systemic amyloidosis and seems to be more frequently affected in immunoglobulin (primary) t han in reactive (secondary) amyloidosis. Amyloid is common in the elde rly. Isolated atrial amyloid, for which a major subunit is the atrial natriuretic peptide, seems to be three times more frequent than senile cardiac amyloid, which is derived from normal prealbumin (transthyret in). Like polyneuropathy, cardiac amyloidosis is a prominent clinical feature of hereditary amyloidosis, namely of the autosomal dominant tr ansthyretin (TTR) type. All 28 cases of TTR amyloidoses reported so fa r were heterozygotes for a single nucleotide change in the gene for TT R that resulted in amino acid substitutions in the mature protein. A n ew TTR genetic variant is reported in a German family where the index patient presented at the age of 63 with anginal pain and arrhythmia. E lectrocardiography was suggestive of a pseudoinfarction pattern, and e chocardiography and cardiac catheterisation showed signs of hypertroph ic nonobstructive cardiomyopathy with increased ventricular filling pr essures and a prominent ''a'' wave. Amyloid of the TTR type was identi fied by immunohistochemistry in the endomyocardial biopsy specimen. Hy brid isoelectric focusing established heterozygosity by showing normal TTR protein and an electrically neutral TTR variant differing from al l known TTR variants so far. The patient died in an accident before in vestigations were complete. Electrophoretic analysis of the plasma fro m his first degree relatives (son, daughter, brother, and mother) iden tified the asymptomatic 22 year old son as an apparently heterozygous carrier of the mutant TTR protein. Comparative tryptic peptide mapping and sequencing showed that isoleucine at position 68 of the amino aci d sequence was replaced by leucine.