PO66 Danon Disease presenting with severe rapidly progressive cardiomyopathy in a Young Paediatric Male Patient: Management Challenges

Case Presentation: A 12-year-old boy presented with a history of attention deficit hyperactivity disorder, mild learning disability, easy fatigability, hepatomegaly, myopia, persistent elevated serum creatine kinase (CK >600U/L), and abnormal liver enzymes. The patient had no known history of genetic diseases in the family. Given the suspicion for a storage disease with multiorgan involvement, he was referred for cardiovascular workup. The ECG showed sinus tachycardia, normal PR interval and deep T-wave inversion in the antero-lateral and inferior leads (Figure 1A). The transthoracic echocardiogram showed severe concentric left ventricular (LV) hypertrophy, normal LV ejection fraction, mildly reduced global longitudinal strain with an “apical sparing” pattern and grade 2 diastolic dysfunction (Figure 1B; Supplementary Material online: Figure S1-S2; Videos S1-S3). On cardiac magnetic resonance (CMR) there was concentric massive LV hypertrophy (19mm in the anterior basal septum, Z-score ≥2; LV mass index 151g/m2) with extensive midwall, mainly lateral, late gadolinium enhancement (LGE), corresponding to ∼15% of the total myocardial mass, and increased native-T1 mapping values (Figure 1C). Genetic testing revealed a heterozygous mutation in the LAMP2 gene [(NM_002294.3) - c.184-2A>T(r.spl)], later discovered to be also present in his mother in familiar cascade testing (who had undiagnosed cardiomyopathy). Accordingly, the diagnosis of Danon Disease was established1. During follow-up, the patient had mild dyspnoea and fatigue (NYHA II). On follow-up CMR (2 years later) (Figure 1 E-F) there was worsening of LV hypertrophy (31mm in the anterior basal septum, LV mass index 274 g/m2), de-novo mild reduced LV ejection fraction (51%) and a significant increase of the LGE extensiveness (54% of the LV mass), with relative sparing of the interventricular septum. Accordingly, an implantable cardioverter-defibrillator device was recommended for sudden cardiac death prevention2,3. The patient is now being followed every 6 months and a full workup for heart transplant has been initiated.