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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 21year-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 publication

DOI

10.1016/j.ymgme.2017.06.008

Type

Journal article

Journal

Mol Genet Metab

Publication Date

02/2018

Volume

123

Pages

177 - 183

Keywords

Autophagy, Danon disease, Hypertrophic cardiomyopathy, LAMP2, Learning difficulties, Obesity, Rapamycin, Thyrotoxicosis, Troponin, Adolescent, Adult, Biomarkers, Cardiomyopathy, Hypertrophic, Child, Disease Management, Female, Glycogen Storage Disease Type IIb, Humans, Male, Pedigree, Prognosis, Troponin I