A CLINICAL, ECHOCARDIOGRAPHIC AND GENETIC-CHARACTERIZATION OF A DANISH KINDRED WITH FAMILIAL AMYLOID TRANSTHYRETIN METHIONINE-111 LINKED CARDIOMYOPATHY

Aims To identify carriers and non-carriers of the mutant transthyretin methionine 111 linked familial amyloid disease, to detect early signs of the restrictive cardiomyopathy and other clinical manifestations c haracteristic of this inheritable disease Methods and Results Out of 1 25 living family members 99 were available for clinical, echocardiogra phic and gen etic examination. Twenty-five family members were heteroz ygous carriers of the mutant transthyretin methionine 111 genotype, wh ile 74 were non-carriers. Among the 25 carriers, none had overt clinic al signs of heart disease. Eight carriers, all above the age of 35, sh owed echocardiographic abnormalities suggestive of developing or manif est restrictive cardiomyopathy. Three had biopsy-verified transthyreti n-related amyloid cardiomyopathy. None of the 15 carriers in the young er age group exhibited aberrant echocardiographic patterns. Nine carri ers had carpal tunnel syndrome as opposed to none of the noncarriers. Conlusion For early detection of familial amyloid cardiomyopathy, echo cardiography is the investigation of choice. The first sign is diastol ic dysfunction detected as an abnormal relaxation pattern. The appeara nce of echocardiographic aberrations solely in the older age group sug gests that the cardiomyopathy is a late onset disease. Carpal tunnel s yndrome appears to be the earliest presenting clinical symptom. A cura tive treatment seems to be an early liver transplantation.