Danon disease

ECG: Sinus rhythm, short PR, delta wave: ventricular pre-excitation; probable left ventricular hypertrophy with increased QRS complex voltages (largely positive Sokolow index);

Comments: Danon disease is a relatively rare glycogenosis due to a deficiency in α-1,4-glucosidase acid that hydrolyzes glycogen into glucose units, resulting in an intra-lysosomal glycogen overload. It affects skeletal, cardiac and respiratory muscles and is associated with intellectual deficit. Symptoms are usually greater and more prevalent in men than in women. The onset of heart disease is progressive with initially a concentric left ventricular hypertrophy which can be substantial without alteration in contractility and subsequently evolving to a dilatation of the cavity leading to severe left ventricular dysfunction altering the prognosis.

As in this patient, the demonstration of a pre-excitation (Wolff-Parkinson-White syndrome) is very common (more often in men than in women). The mechanisms explaining this increased incidence in pre-excitation are poorly understood. In an animal model of Danon disease, the fibrous sheath that normally electrically isolates the ventricles from the atria is interrupted by myocytes rich in glycogen which constitute the substrate for accessory electrical connection and ventricular pre-excitation.

Take-home message: The demonstration of ventricular pre-excitation (Wolff-Parkinson-White syndrome) in a young patient with hypertrophic cardiomyopathy should evoke the diagnosis of Danon disease.