Severe Myopathy Following Heart Transplantation in a Patient with Danon Disease

Introduction A patient with Danon disease develops a severe myopathy with rhabdomyolysis following heart transplantation (HT). Case Report A 20-year-old man affected by Danon disease with mild muscular affection and refractory heart failure underwent HT in May 2020. He presented an uneventful initial course with early withdrawing of inotropic and ventilatory support. Immunosuppressant therapy consisted of: Basiliximab, Mycophenolate, Methylprednisolone 1000mg followed by 1 mg/kg the next week and Tacrolimus started on the third day post-HT. A week after HT he presented a rapidly progressive muscle weakness with hypercapnic respiratory failure and decreased level of consciousness, requiring invasive mechanical ventilation. Initial differential diagnosis included central nervous affection (tacrolimus toxicity versus infection) and peripheral muscular impairment. He underwent CT scan and cerebrospinal fluid analyses with no abnormalities. Blood test demonstrated an intense rhabdomyolysis with creatinine kinase elevation up to 3904 U/L and myoglobin 41287 ng/mL. Biceps muscular biopsy confirmed significant necrosis with regeneration phenomena and PAS positives vacuoles (related to his underlying Danon disease). Since steroid use has been reported to accelerate myopathy in patients with Danon disease, Methylprednisolone was withdrawn on day 12 post-HT and a complementary third Basiliximab dose was administered to prevent early rejection. Creatinine kinase values decreased dramatically after steroid removal and remained normal during follow-up. In order to improve functional rehab, he underwent intensive physical therapy being weaned off the ventilator on post HT day 21. A first endomyocardial biopsy showed no significant rejection. The patient was finally discharged home with normal ventilation and a great improvement in peripheral muscular strength. He is currently undergoing monthly rejection follow-up biopsies with no evidence of cellular or antibody-mediated rejection at 5 months post-HT. Summary Danon disease can lead to severe cardiomyopathy requiring HT. High-doses of corticosteroid therapy have been described as a potential cause of skeletal myopathy exacerbation, even in recipients with mild symptoms before HT. Thus, steroid use surveillance is needed in patients with Danon disease following HT.