When Hypertrophy Hides a Storage Disease

Description of Clinical Presentation: A 13-year-old female was referred for cardiological evaluation as part of a family screening program after the death of her mother at the age of 32 from rapidly progressive heart failure secondary to dilated cardiomyopathy of unknown etiology. The medical history of the remaining family members was not available.
The patient was asymptomatic with no significant past medical history.
Resting electrocardiogram showed short PR tract, markedly increased QRS voltages, deep T-wave inversion in the precordial and inferior leads, and diffuse ST-segment abnormalities consistent with left ventricular overload.
Laboratory testing revealed mildly elevated creatine kinase (400 U/L) with normal troponin levels.

Diagnostic Techniques and Their Most Important Findings: Transthoracic echocardiography revealed asymmetric left ventricular hypertrophy, with maximal wall thickness at the lateral wall and interventricular septal thickness within normal limits. Left ventricular systolic function was preserved (LVEF 65%), left atrial size was normal, and there was no evidence of valvular disease. Increased endocardial trabeculation was observed in both ventricles.

Cardiac Magnetic Resonance (Figures 1 and 2): The left ventricle was not dilated and demonstrated asymmetric hypertrophy, with maximal wall thickness of 19 mm at the lateral wall and 10 mm at the interventricular septum. Global systolic function was preserved. Prominent endocardial trabeculation was noted in both ventricles. T2 mapping values were increased (56 ± 3 ms; normal < 50 ms), as were T1 mapping values (up to 1150 ± 25 ms; normal < 1020 ms), both predominantly involving the most hypertrophic segments of the lateral wall, with relative sparing of the mid-basal septum. Extracellular volume (ECV) was also expanded, reaching 32%. Diffuse late gadolinium enhancement (LGE) was observed, predominantly involving the most hypertrophic segments in the lateral wall, accounting for 8% of the total myocardial mass.
The most likely differential diagnoses included Danon disease, Fabry disease, PRKAG2-related cardiomyopathy, and sarcomeric hypertrophic cardiomyopathy.

Genetic testing was decisive, revealing a likely pathogenic mutation in the LAMP2 gene, thus establishing the diagnosis of Danon disease.

Learning Points from this Case: In young patients with suggestive ECG findings and a family history of early cardiomyopathy, cardiac magnetic resonance plays a fundamental role in guiding the diagnosis, particularly for metabolic or storage diseases, while genetic testing is essential to confirm the diagnosis and direct family screening.

Clockwise: Phase Sensitive Inversion Recovery (PSIR) short-axis view, showing intramyocardial LGE in the mid-lateral wall; four-chamber cine Steady-State Free Precession (SSFP) view demonstrating asymmetric hypertrophy predominantly involving the anterolateral wall; three-chamber PSIR view with basal inferolateral intramyocardial LGE and four-chamber PSIR view demonstrating diffuse LGE of the lateral wall.
Right: T2 mapping; Left: T1 mapping in a four-chamber view, both showing markedly elevated T2 and T1 values in the lateral wall of the left ventricle with relative sparing of the basal–mid interventricular septum.