Heterogeneity in a large pedigree with Danon disease: Implications for pathogenesis and management

Jonathan C. P. Roos, Matthew J. Daniels, Elizabeth Morris, Hanna I. Hyry, Timothy M. Cox

Research output: Contribution to journalArticleAcademicpeer-review


Background: Danon disease is an X-linked disturbance of autophagy manifesting with cognitive impairment and disordered heart and skeletal muscle. After a period of relative stability, patients deteriorate rapidly and may quickly become ineligible for elective heart transplantation - the only life-saving therapy. Methods: We report a large pedigree with diverse manifestations of Danon disease in hemizygotes and female heterozygotes. Results: Malignant cardiac arrhythmias requiring amiodarone treatment induced thyroid disease in two patients; intractable thyrotoxicosis, which enhances autophagy, caused the death of a 21 year-old man. Our patients also had striking elevation of serum troponin I during the accelerated phase of their illness (p<0.01) and rising concentrations heralded cardiac decompensation. We argue for changes to cardiac transplantation eligibility criteria. Conclusion: Danon disease causes hypertrophic cardiomyopathy - here we propose a common pathophysiological basis for the metabolic and structural effects of this descriptive class of heart disorders. We also contend that troponin I may have prognostic value and merits exploration for clinical decision-making including health warning bracelets. Rapamycin (Sirolimus®), an approved immunosuppressant which also influences autophagy, may prove beneficial. In the interim, while new treatments are developed, a revaluation of cardiac transplantation eligibility criteria is warranted.
Original languageEnglish
Pages (from-to)177-183
JournalMolecular Genetics and Metabolism
Issue number2
Publication statusPublished - 2018
Externally publishedYes

Cite this