Hypertrophic Cardiomyopathy - HCM - PRKAG2

A subset of familial HCM patients with conduction abnormalities, particularly progressive atrioventricular block, Wolff-Parkinson-White syndrome (WPW) and atrial fibrillation have been attributed to mutations in the genes encoding the γ2 regulatory subunit of adenosine monophosphate (AMP)-activated protein kinase (PRKAG2) and lysosome-associated membrane protein 2 (LAMP2). 
Mutations in PRKAG2 cause constitutive activation of AMPK associated with increased glycogen content of skeletal muscle cells in animal models. Affected patients develop severe cardiac hypertrophy with supraventricular tachyarrhythmias and progressive atrioventricular block that necessitate aggressive control of arrhythmias and pacemaker insertion. The histopathology of PRKAG2 mutations shows glycogen accumulation in myocytes without myocyte disarray.