Danon Disease (Rare Cardiomyopathy) Can Progress Rapidly

A rare genetic heart disorder called Danon Disease progresses rapidly and is often deadly in young people, according to a new study.

The recently recognized disease is a type of cardiomyopathy, or heart muscle disorder, linked to genetic mutations in the lysosome-associated membrane protein gene (LAMP2). Until now, the natural course of the disease was unclear.

Danon disease is a rare genetic disorder characterized by an X-linked dominant inheritance pattern, as a result of which males are more severely affected than females. Among boys, the key features are diseased heart muscle (cardiomyopathy), weakness of the body muscles (skeletal myopathy) and intellectual disability ranging from mild learning problems to mental retardation. In many males, the disease progresses until a heart transplant is required or death occurs in the second to third decade of life. Females are also affected, although usually more mildly, and often onset is delayed until they reach adulthood.

Other features include heart arrhythmias, which can lead to a need for medications or a pacemaker, and eye disease affecting the retina; the retinal disease does not always affect vision. Danon disease is not usually evident at birth unless blood tests are done in a suspected case (i.e. a son born to a mother known to have the disease).

Researchers from the Minneapolis Heart Institute Foundation studied seven people diagnosed with Danon disease when they were 7 to 17 years old. In six of them, diagnosis was made as the result of a heart murmur, family screening and findings on routine electrocardiogram tests or from such symptoms as chest pain and fainting. In one person, atrial fibrillation, an abnormal heart rhythm, led to the diagnosis.

Within nine years of diagnosis, on average, all seven had encountered serious problems. One person had a heart transplant, and four died of acute or progressive heart failure. Their deterioration was often rapid, going from having few or no symptoms to end-stage heart failure within as little as six months.

The other two people in the study had sudden, unexpected, major arrhythmic events, and one of them died suddenly from ventricular fibrillation — very rapid, uncoordinated contractions of the ventricles — that was not controlled by an implantable cardioverter defibrillator.

All seven developed problems with contraction of their left heart ventricle, called left ventricular systolic dysfunction. All seven had a defibrillator implanted, but in five of them, the devices failed to prevent lethal tachyarrhythmias — excessively rapid heartbeat accompanied by irregular heartbeat.

The final electrocardiograms examined by the researchers showed significant enlargement of the left ventricle in all seven, the study reported.

“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 recognized genetic cardiomyopathy,” the researchers wrote. “LAMP 2 mutations cause a particularly profound and accelerated cardiac disease process characterized 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.”

The finding “establishes the importance of molecular diagnosis and underscores the utility of genetic testing,” they concluded.

Source: Wikipedia and JAMA, March 24, 2009

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