Recently identified genetic heart disorder often deadly for young patients


A study that included young patients with a recently recognised rare type of cardiomyopathy linked to a genetic mutation finds that progression of this disease may be rapid and often results in early death, according to a study in the 25 March, 2009 issue of Journal of the American Medical Association.

Mutations in the lysosome-associated membrane protein gene (LAMP2, known as Danon disease) produce a cardiomyopathy in young patients that clinically is similar to severe hypertrophic cardiomyopathy. However, the natural course of Danon disease has been unclear, according to background information in the article.

Dr Barry J Maron, Minneapolis Heart Institute Foundation, USA, and colleagues assessed the natural history associated with LAMP2 cardiomyopathy and the outcomes of diagnostic and management strategies. The study included seven patients (six boys) who were ages 7-17 years at the time of diagnosis with LAMP2 mutations. Clinical diagnosis in six patients occurred as a result of a heart murmur, family screening and findings on routine electrocardiogram or by symptoms (chest pain or fainting) and, in one patient, by atrial fibrillation.

During the subsequent average time of 8.6 years after diagnosis, each of the seven patients experienced serious adverse clinical consequences by 14 to 24 years of age (average, 21 years). Four patients died of acute or progressive heart failure, and one patient underwent heart transplantation. Clinical deterioration was often rapid, with the time interval from clinical stability with little or no symptoms to end-stage heart failure as brief as six months. Two other patients experienced sudden unexpected major arrhythmic events, with one patient dying suddenly (age 14 years) from ventricular fibrillation that was not responding to implantable cardioverter-defibrillator (ICD) therapy.

All seven patients developed left ventricular systolic dysfunction. All patients had received ICDs, which ultimately failed to terminate lethal ventricular tachyarrhythmias (an excessively rapid heartbeat accompanied by an irregular heartbeat) in five patients. The most recent echocardiographic studies obtained of the patients demonstrated marked left ventricular hypertrophy in each. Postmortem examination of two hearts showed massive cardiac hypertrophy.

“The clinical course of these seven patients with LAMP2 mutations provides important insights regarding molecular diagnosis as well as the natural history, pathophysiology, and clinical implications of this recently recognised genetic cardiomyopathy. LAMP2 mutations cause a particularly profound and accelerated cardiac disease process characterised by clinical deterioration and early death, perhaps representing one of the most lethal cardiomyopathies in young and usually male patients. Such an outcome occurred in the patients in our study despite application of the most contemporary treatment strategies, including the ICD …” the authors wrote. “The early experience with the distinctive natural history and prognosis of patients with LAMP2 mutations establishes the importance of molecular diagnosis and underscores the utility of genetic testing.”