Cardiomyopathy in Swedish patients with the Gly53Glu and His88Arg transthyretin variants

Abstract

We report two new amyloidogenic transthyretin (TTR) variants detected in the Swedish population. One variant was previously unknown, while the other has been described in a French family. In Swedish patients, both variants have caused late-onset cardiac amyloidosis characterised by heart failure. In both cases, the diagnosis was determined by the detection of amyloid deposits in skin and/or rectal biopsies and identification of TTR mutations by genetic analysis. The index case of the previously unknown mutation (ATTR His88Arg) was a 66-year-old Swedish man, who sought medical attention for increasing dyspnea. Echocardiographic examination disclosed a restrictive cardiomyopathy, and subsequent examinations disclosed TTR amyloidosis. The patient is alive with moderate symptoms one year after the onset of disease. The index case for the new Swedish mutation (ATTR Gly53Glu) is a woman who sought medical attention at the age of 57 because of increasing dyspnea. Echocardiographic examination disclosed a hypertrophic cardiomyopathy with diastolic impairment. The diagnosis of systemic amyloidosis was made by fat aspiration biopsy and histopathology. The patient developed severe intractable heart failure, with pulmonary effusion and ascites. She died four years after the onset of her disease of intractable heart and kidney failure. Post mortem examination of biopsy specimens and blood revealed TTR amyloid deposits and the ATTR Gly53Glu mutation was detected.

Keywords:

• Amyloidosis–hereditary
• transthyretin
• cardiomyopathy

Abbreviations
ATTR	=	variant transthyretin;
DHPLC	=	denaturing high performance liquid chromatography
HPLC	=	high performance liquid chromatography
PCR	=	polymerase chain reaction
TTR	=	transthyretin

Abbreviations
ATTR	=	variant transthyretin;
DHPLC	=	denaturing high performance liquid chromatography
HPLC	=	high performance liquid chromatography
PCR	=	polymerase chain reaction
TTR	=	transthyretin