The Cardiological Lysosomal Storage Disorder - Danon Disease

Summary of Disease

Danon disease is a rare genetic disorder that affects the heart.¹ It is a type of lysosomal storage disorder, specifically causing defects in the membrane of lysosomes.¹ Lysosomes are organelles in the cell that break down large molecules for the cell to readily use for various functions; therefore, these defects cause malfunctions in organs that can lead to death.²

Etiology and Pathology

The defects in the lysosomal membrane are caused by mutations in the LAMP2 gene. The LAMP2 gene encodes the lysosomal-associated membrane protein-2 (LAMP-2), which plays an unclear role in the membrane of lysosomes.³ Danon disease has an X-linked dominant inheritance pattern, meaning that men are more likely to be affected by the disease and have significantly worse symptoms than women.⁴ Due to the rarity and limited research on the disorder, the age of onset for males and females is unknown; however, on average, males live to age nineteen while women live to age thirty-four.³

The rarity of Danon disease restricted the amount of research done on the disorder.⁵ The largest-scale study about Danon disease had 82 patients from 36 different families.⁵ From this study, the age of onset found was 12.1 ± 6.5 years for males and 28.1 ± 15 years for females.⁵ The average age of diagnosis was 13.5 ± 7.0 years for males and 31.4 ± 15.4 years for females.⁵ The study also found that the mutations were all mostly different from one another, with some being frameshift or stop codon mutations, but they all caused a deficiency of the LAMP-2 protein.⁵ The study provided clarity and more information about the effects of Danon disease on males and females, but the rarity of the disease causes future research to be difficult.⁵

Symptoms

The symptoms of Danon disease vary from person to person and between genders.⁴ Men usually exhibit muscle problems such as awkward motor skills or difficulty walking, as well as mild intellectual disability, at a young age.¹ Females typically do not have any visible symptoms at a young age, but symptoms will quickly arise as they age.⁴ Some general and prevalent symptoms for both genders are the weakening of heart muscles (cardiomyopathy) and skeletal muscles (skeletal muscle myopathy), and intellectual disability.¹ Other less common symptoms include chest palpitations, abnormal heartbeat (arrhythmia), and general chest pain.³

Diagnosis

Healthcare professionals typically diagnose people suspected of having Danon disease by analyzing the patient’s medical history and symptoms, as well as a physical and laboratory test.¹ Danon disease does not show any significant symptoms when the patient is a baby or infant, so healthcare professionals diagnose patients who may have inherited the disorder, such as the children of parents who have Danon disease.⁴

Treatment and Prognosis

Treating the patient focuses on addressing the various symptoms each patient experiences, which may require an entire team of specialized doctors.^1,6 Addressing symptoms is especially important since the symptoms can exacerbate rapidly and cause sudden death.¹ Unfortunately, there is no specific therapy or treatment that can treat the effects of Danon disease, but cardiac transplantation may lengthen the patient’s life.^1,6

Support Groups

Organizations and support groups for Danon disease include the Association for Glycogen Storage Disease, the Cardiomyopathy Association, and the Children’s Cardiomyopathy Foundation.¹ Due to the rarity of Danon disease, these groups are excellent resources to connect with other families with Danon disease patients and receive advice to deal with similar difficult circumstances.¹

Sreethan Vuppala

References

1. Danon disease. Genetic and Rare Diseases Information Center. Published July 12, 2016. Accessed March 25, 2022. https://rarediseases.info.nih.gov/diseases/9730/danon-disease.

2. Rajkumar V, Dumpa V. Lysosomal storage disease. StatPearls [Internet]. Published January 28, 2022. Accessed March 25, 2022. https://www.ncbi.nlm.nih.gov/books/NBK563270/#:~:text=Lysosomal%20storage%20diseases%20(LSDs)%20are,to%20great%20morbidity%20and%20mortality.

3. MedlinePlus. Danon disease. MedlinePlus. Published November 26, 2021. Accessed March 25, 2022. https://medlineplus.gov/genetics/condition/danon-disease/.

4. Danon disease. NORD (National Organization for Rare Disorders). Published March 12, 2018. Accessed March 25, 2022. https://rarediseases.org/rare-diseases/danon-disease/.

5. Boucek D, Jirikowic J, Taylor M. Natural history of Danon disease. Genetics in Medicine. 2011;13(6):563-568. doi:10.1097/gim.0b013e31820ad795

6. Di Nora C, Miani D, D'Elia AV, et al. Heart transplantation in Danon disease: Long term single centre experience and review of the literature. Eur J Med Genet. 2020;63(2):103645. doi:10.1016/j.ejmg.2019.04.002

Cite This Article:

Vuppala S., Lee, K., Dmitriev, A. The Cardiological Lysosomal Storage Disorder - Danon Disease. Illustrated by J. Duchscher. Rare Disease Review. September 2024. DOI: 10.13140/RG.2.2.33339.94246