International Consensus on Differential Diagnosis and Management of Patients With Danon Disease: JACC State-of-the-Art Review

J Am Coll Cardiol. 2023 Oct 17;82(16):1628-1647. doi: 10.1016/j.jacc.2023.08.014.

Abstract

Danon disease is a rare X-linked autophagic vacuolar cardioskeletal myopathy associated with severe heart failure that can be accompanied with extracardiac neurologic, skeletal, and ophthalmologic manifestations. It is caused by loss of function variants in the LAMP2 gene and is among the most severe and penetrant of the genetic cardiomyopathies. Most patients with Danon disease will experience symptomatic heart failure. Male individuals generally present earlier than women and die of either heart failure or arrhythmia or receive a heart transplant by the third decade of life. Herein, the authors review the differential diagnosis of Danon disease, diagnostic criteria, natural history, management recommendations, and recent advances in treatment of this increasingly recognized and extremely morbid cardiomyopathy.

Keywords: Danon disease; LAMP-2; cardiomyopathy; lysosomal storage disease; rare genetic disorder.

Publication types

  • Review
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Cardiomyopathies* / diagnosis
  • Cardiomyopathies* / genetics
  • Cardiomyopathies* / therapy
  • Consensus
  • Diagnosis, Differential
  • Female
  • Glycogen Storage Disease Type IIb* / complications
  • Glycogen Storage Disease Type IIb* / diagnosis
  • Glycogen Storage Disease Type IIb* / genetics
  • Heart Failure* / diagnosis
  • Humans
  • Lysosomal Storage Diseases
  • Lysosomal-Associated Membrane Protein 2 / genetics
  • Male
  • Muscular Diseases

Substances

  • Lysosomal-Associated Membrane Protein 2

Supplementary concepts

  • Vacuolar myopathy