What Is Danon Disease (DD)?

DD is a rare, often fatal form of genetic cardiomyopathy.1

Danon disease is caused by mutations in the lysosomal-associated membrane protein 2 (LAMP2) gene. The LAMP-2 protein is an important part of cellular autophagy—the process by which cells break down and destroy or remove old, damaged, or abnormal materials within the cell—and the absence or reduction of the LAMP-2 protein can result in a disruption of the autophagy process.1

While the exact prevalence of DD is not known, it is estimated that as many as 5% of all pediatric hypertrophic cardiomyopathy cases are the result of Danon disease.1

DD presentation varies by sex, with males experiencing earlier onset and a more severe phenotype.2 Additionally, race is not believed to be a predictive factor in DD.2

385

estimated new US cases annually3*

14,941

estimated total US cases in 20233*

12.1 (±6.5)

Mean age (SD) of symptom onset in males4

28.1 (±15)

Mean age (SD) of symptom onset in females4

*Estimate derived from Rocket epidemiology model based on published data.
SD, standard deviation.

ATTENTION: Use ICD-10 diagnostic code E74.05 LAMP-2 deficiency Danon disease

Triad of Symptoms

Danon disease is characterized by a triad of cardiac, skeletal muscle, and neurological symptoms.4 There are other less prevalent symptoms that may present including retinal disease.4

COMMON SYMPTOMS OF DANON DISEASE
Male
Female
Cardiac Phenotype2
HCM
HCM or DCM
Concomitant WPW2
69%
27%
Learning Deficit1,2,4
Mild to moderate
Mild, if present
Motor Delays/Muscle Weakness2,5
Yes, predominantly in the trunk/upper body/face
Mild or asymptomatic/muscle cramping
Male

Cardiac Phenotype2 HCM

Concomitant WPW2 69%

Learning Deficit1,2,4 Mild to moderate

Motor Delays/Muscle Weakness2,5 Yes, predominantly in the trunk/upper body/face

Female

Cardiac Phenotype2 HCM or DCM

Concomitant WPW2 27%

Learning Deficit1,2,4 Mild, if present

Motor Delays/Muscle Weakness2,5 Mild or asymptomatic/muscle cramping

DCM, dilated cardiomyopathy; HCM, hypertrophic cardiomyopathy; WPW, Wolff-Parkinson-White syndrome.

The Need for Timely Diagnosis

Danon disease (DD) is progressive and can lead to sudden or early death.2,4,5

Rapid progression

  • DD can rapidly progress to heart failure requiring transplant4,5
  • The mean age (SD) at heart transplant is 20.8 (±6.7) years for males, and 32.3 (±14.5) years for females4
  • Pregnancy can precipitate heart failure and death in females5

Significant cardiovascular complications

  • Stroke is common in patients with DD and may occur in young adulthood (20-30 years of age)5
  • Pregnancy can precipitate the onset of the DCM phenotype of DD in females5

Sudden or early death

Mean age of death is 20 years of age for males and 40 years of age for females4

DCM, dilated cardiomyopathy; SD, standard deviation.

Genetic testing in patients with suspected inherited cardiomyopathy can expedite the path to diagnosis of DD.6
Testing for Danon Disease (DD)

When inherited cardiomyopathy is suspected, genetic testing can reduce the time to diagnosis, prevent misdiagnoses, and inform disease management.6

A positive test for a mutated LAMP2 gene in the context of clinical presentation is the definitive indicator of DD.7

  • Genetic testing for LAMP2 is often included in cardiomyopathy, lysosomal disorders, and myopathy testing panels5
  • 11% of patients who would have been missed using condition-specific panels were identified with comprehensive testing8
  • Inclusion of LAMP2 on neurodevelopmental panels and screening for family planning could5:
    • Identify DD patients earlier
    • Recognize and detect DD symptoms, especially in females who may present differently from males
    • Reduce the risk of transmitting a mutated gene
Guidelines recommend consideration of genetic assessment in patients with genetic or inherited cardiomyopathies.9*

*The 2022 American Heart Association (AHA), American College of Cardiology (ACC), Heart Failure Society of America (HFSA), and Heart Rhythm Society (HRS) guidelines recommend consideration of genetic assessment in patients with cardiomyopathies (CM) and heart failure.9
LAMP-2, lysosomal-associated membrane protein 2.

Learn more about the importance of genetic testing for Danon disease and other conditions
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References: 1. Brambatti M, Caspi O, Maolo A, et al. Danon disease: gender differences in presentation and outcomes. Int J Cardiol. 2019;286:92-98. 2. D’Souza RS, Levandowski C, Slavov D, et al. Danon disease: clinical features, evaluation, and management. Circ Heart Fail. 2014;7(5):843-849. 3. Rocket Pharmaceuticals. Data on file. Danon Disease. 4. Boucek D, Jirikowic J, Taylor M. Natural history of Danon disease. Genet Med. 2011;13(6):563-568. 5. Cenacchi G, Papa V, Pegoraro V, et al. Review: Danon disease: review of natural history and recent advances. Neuropathol Appl Neurobiol. 2020;46(4):303-322. 6. Scherr CL, Kalke K, Ramesh S, et al. Integrating clinical genetics in cardiology: current practices and recommendations for education. Genet Med. 2022;24(5):1054-1061. 7. Hong KN, Eshraghian EA, Arad M, et al. International consensus on differential diagnosis and management of patients with Danon disease: JACC state-of-the art review. J Am Coll Cardiol. 2023;82(16):1628-1647. 8. Dellefave-Castillo LM, Cirino AL, Callis TE, et al. Assessment of the diagnostic yield of combined cardiomyopathy and arrhythmia genetic testing. JAMA Cardiol. 2022;7(9):966-974. 9. Heidenreich PA, Bozkurt B, Aguilar D, et al. 2022 AHA/ACC/HFSA Guideline for the Management of Heart Failure: A Report of the American College of Cardiology/American Heart Association Joint Committee on Clinical Practice Guidelines. Circulation. 2022;145(18):e895-e1032.