Cardiovascular magnetic resonance findings in a case of Danon disease
© Piotrowska-Kownacka et al; licensee BioMed Central Ltd. 2009
Received: 06 January 2009
Accepted: 29 April 2009
Published: 29 April 2009
Danon disease is a rare X-linked dominant lysosomal glycogen storage disease that can lead to severe ventricular hypertrophy and heart failure. We report a case of Danon disease with cardiac involvement evaluated with cardiovascular magnetic resonance, including late gadolinium enhancement and perfusion studies.
A 19 year old male with no previous history of heart disease was admitted with rest dyspnoea, found to be due to acute heart failure. He had felt fatigued with progressive limitation of exercise tolerance over the preceding 3 months. Symptoms were exacerbated by an upper respiratory tract infection one month before hospitalization. The patient was treated with antibiotics without noticeable improvement. The patient's mother had died suddenly at the age of 44 with a dilated cardiomyopathy of unknown cause for which she had had a pacemaker implanted.
On admission, the patient was cachectic with a body mass index of 17 and in poor general condition, with rest dyspnoea, tachypnoea of 30/minute and tachycardia of 130/minute. His liver was enlarged, there was evidence of pulmonary oedema and a systolic murmur, maximal at the apex.
Blood analysis showed elevated liver enzymes (aspartate aminotransferase 192 units/L; alanine aminotransferase 400 u/L and creatine kinase 510 u/L) and mildly elevated Troponin I and C-reactive protein levels. Chest X-ray confirmed pulmonary oedema and showed an enlarged heart shadow. Sinus tachycardia and left bundle branch block with QRS duration >200 ms were present on electrocardiogram.
Echocardiography on admission revealed significantly enlarged left ventricle and both atria, severe hypertrophy of both ventricles muscle without left ventricular outflow tract (LVOT) obstruction. Moderate tricuspid and severe mitral valve insufficiency, decreased left ventricular (LV) ejection fraction to 30% with global hypokinesis were observed.
The patient was referred for cardiovascular magnetic resonance (CMR), which was performed on a 1.5 T system with 4 element torso coil. Oxygen was supplied by mask throughout the study at a flow rate of 3 l/min. Function was assessed with steady state free precession (SSFP) sequence in short axis slices covering the ventricles and in 4-chamber, 2-chamber and LVOT orientations. Perfusion was assessed at rest only in 8 short axis slices using a gradient echo sequence with inversion recovery during and after intravenous administration of Gadopentate dimeglumine (Gd-DTPA, 0,15 mmol/kg). Late gadolinium enhancement (LGE) images were obtained after 10–20 min in short axis and 4 chamber orientations. Inversion time was adjusted to null the signal from normal LV myocardium.
The patterns of LGE and perfusion deficit were atypical for sarcomeric hypertrophic cardiomyopathy, and based on the CMR findings, myocarditis was considered unlikely. An ischaemic cause of the subendocardial LGE was considered, but the lack of correspondence with typical coronary territories and the combination with the severe hypertrophy of affected segments made this unlikely. Other causes of hypertrophy, including amyloidosis and Anderson-Fabry disease were also considered, but the LGE pattern did not seem typical. In Anderson-Fabry disease, the basal segments are predominantly affected. In amyloidosis, LGE can include subepicardial layers, but with a characteristic "zebra" pattern, and early decline of contrast levels in the blood stream.
Danon disease is a rare X – linked dominant, lysosomal glycogen storage disease that can lead to severe cardiac hypertrophy and heart failure especially in affected males. It was described first in 1981 in two boys by Moris J. Danon . Mutation on LAMP2 gene, located on chromosome X, than encodes LAMP2 protein was identified as a cause of Danon Disease . The X-linked disease should be considered in young males with cardiac hypertrophy and coexisting mental retardation/learning difficulties, skeletal myopathy or muscle weakness [3, 4]. In some cases ophthalmic abnormalities  or WPW syndrome were reported [3, 6]. Females who carry the mutation in the LAMP2 gene on chromosome X could develop dilated or hypertrophic cardiomyopathy in their early 40s. Mental retardation or skeletal myopathy can be present in female carriers, but less commonly than in affected males .
Written informed consent was obtained from the deceased patient's next of the kin (sister) for publication of this case report and accompanying images. A copy of the written consent is available for review by the Editor-in-Chief of this journal.
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