What Is Danon Disease? 

Danon disease is a rare genetic condition that affects cardiac (heart) and skeletal muscle. Some people with Danon disease also have an intellectual disability.1 Many genetic disorders are named after the physician who first reported them. In this case, the disease was named after Dr Moris Danon, who first described symptoms of the disease in two teenage boys in 1981.2

Learning that your child has Danon disease can feel overwhelming. This article aims to provide you with all you need to know as you consider what the diagnosis means for your child and family. 


Danon disease is a rare genetic lysosomal storage disease. It is caused by changes in the lysosome-associated membrane 2 (LAMP2) gene.1

Lysosomes are small components found within cells that break down waste materials. Lysosomal storage diseases arise due to errors in single genes. Typically, the genes involved tell cells how to make enzymes or proteins that are required for the normal functioning of lysosomes and, thus, the normal processing of waste. The accumulation of waste products within lysosomes can cause a range of symptoms in different organs and tissues depending on the individual disease in question.3

Danon disease is one of over 70 lysosomal storage diseases that have so far been discovered.3  It classically causes problems with cardiac muscle (the muscle of the heart), skeletal muscle (muscles that connect to bones that allow us to perform normal movement), and intellect.1 Danon disease affects those assigned males at birth (AMAB) and those assigned females at birth (AFAB). Symptoms are usually more significant in those AMAB.1 

This article will explain the genetic changes underlying Danon disease and how it impacts those who are affected. We will also explore current management approaches and the support available to families. 

The genetics of danon disease

We all have two copies of every gene in each of our cells. Our genes are stored in bookcases called chromosomes. Since we have two copies of every gene, it makes sense that we, therefore, have two copies of every chromosome.4

Humans have 23 pairs of chromosomes. 22 of these pairs are matching, with pairs carrying copies of the same genes. Our sex chromosomes are the exception to this role. Our birth sex is determined by whether we carry two X chromosomes (meaning we are birth-assigned female) or one X and one Y chromosome (meaning we are birth-assigned male).4

The LAMP2 gene is found on the X chromosome. This means that Danon disease is described as an X-linked genetic disorder.1

Those who are AMAB will have one copy of the LAMP2 gene, which they inherited from their birthing parent. Their other sex chromosome will be a Y chromosome, which they inherit from their non-birthing parent. Those who are AFAB will have two copies of the X chromosome, receiving one from each of their biological parents. They will, therefore, have two copies of the LAMP2 gene.

The LAMP2 gene tells cells how to make the LAMP2 protein, which is needed for lysosomes to function normally.5 If there is a change in the genetic code (DNA) that makes up the LAMP2 gene, this means that the protein is not made correctly. In most cases, the mistake means that the protein is not made at all, so lysosomes are not able to process waste materials normally.5 In some cases, the mistake may simply result in a protein that is misshapen and works less well.1 The latter will usually result in milder symptoms. Over 160 different errors in the LAMP2 gene have been identified in people with Danon disease.1

Since people AFAB have two X chromosomes, if one of their LAMP2 genes carries an error, it is usually the case that their second copy will be normal. In comparison, people with AMAB will only have one abnormal copy of the gene. Therefore, people with AMAB generally have more severe symptoms of Danon disease because they do not have a second, normal copy of the gene that can partially compensate for the faulty copy. 

For reasons that we don’t completely understand, the error in LAMP2 seems to affect the heart and skeletal muscle most severely, leading to an accumulation of waste products and glycogen (stored glucose) within these cells.5 

If your child has been diagnosed with Danon disease, speak to a genetic counsellor who will be able to help you understand the risk to future children or other children that you already have.6

What are the signs and symptoms of danon disease?

For the reasons discussed, those who are AMAB tend to display more severe symptoms of Danon disease. For this reason, we shall discuss symptoms found in AMAB and AFAB people in turn. 

Symptoms in AMAB patients

Danon disease is often associated with a classical triad of cardiomyopathy (disease of the heart muscle), skeletal myopathy (muscle weakness) and intellectual disability.6 This combination is more common in those who are AMAB since the condition generally results in more severe symptoms in these people. 

Cardiac symptoms in AMAB patients

  • Cardiomyopathy - almost all people with Danon disease who are AMAB will develop some degree of cardiomyopathy.5 Cardiomyopathies are conditions affecting the heart muscle, which causes it to become thickened, dilated, or stiff. This makes it harder for the heart to pump blood effectively.7 The cardiomyopathy that occurs in Danon disease is usually hypertrophic cardiomyopathy, which causes the walls of the heart to become thickened.6 Unfortunately, it is typical for AMAB people to develop heart failure and require a heart transplant in their teens or twenties.6 Signs and symptoms associated with hypertrophic cardiomyopathy include:1,7,8
    • Fatigue
    • Shortness of breath
    • Ankle swelling
    • Chest pain or tightness, especially after exercise
    • The presence of certain murmurs on examination
  • Arrhythmias (abnormal heart rhythms) - over 80% of AMAB patients experience abnormal electrical activity within the heart.6 This may not cause any symptoms, but an abnormal heartbeat may cause episodes of dizziness, collapse, and palpitations. Unfortunately, severe abnormalities sometimes result in sudden cardiac death.6 Many people AMAB will show evidence of abnormal electrical activity on ECG testing. The most common abnormality is a unique pattern that is itself called Wolff-Parkinson-White syndrome. This pattern is seen on the ECGs of almost half of those who are AMAB at presentation.6

Skeletal myopathy in AMAB patients

80-90% of people AMAB with Danon disease experience progressive muscle weakness that typically affects larger muscles of the back, neck, shoulders, and upper arms and legs.6 The impact on function can vary, but common problems include difficulty raising the arms or getting up from a chair. Most retain the ability to walk.1 Often, levels of a muscle enzyme called creatinine kinase (CK) will be elevated.6

Intellectual disability in AMAB patients

Around 80% of people with AMAB will have a degree of intellectual disability if they have a diagnosis of Danon disease.6 This is usually mild, and most of these people will be able to read, hold employment and live independently.1 Other issues affecting behaviour and mental health have been reported amongst some AMAB individuals with Danon disease.6

Other systemic symptoms in AMAB patients

Danon disease causes retinopathy (disease of the retina - a structure at the back of the eye which detects light) in around 20% of people AMAB. This can result in problems with vision.6 Most people with AMAB will have liver problems, such as an enlarged liver, associated with Danon disease. These may not cause any symptoms. Around half will have respiratory involvement, which can be represented by shortness of breath, coughing, or wheezing.5

Symptoms in AFAB patients

People with Danon disease who are AFAB generally have a later onset of symptoms and a less severe form of the condition.1 Cardiac symptoms typically predominate.6

Cardiac symptoms in AFAB patients

  1. Cardiomyopathy - cardiomyopathy affects over 70% of people AFAB with Danon disease. In contrast to the hypertrophic cardiomyopathy usually seen in AMAB people, 30-50% of AFAB people will develop dilated cardiomyopathy.6 This causes the chambers of the heart to become enlarged, making it more difficult for the heart to pump blood effectively.7 The remainder of cardiomyopathy cases within this group are hypertrophic cardiomyopathies.6 Symptoms are broadly similar across different cardiomyopathies and are often related to resultant heart failure. Typical symptoms include shortness of breath, fatigue, ankle swelling and chest pain or tightness.7 Around one-fifth of AFAB people who develop cardiomyopathy will ultimately require a heart transplant.6
  1. Arrhythmias (abnormal heart rhythms) - 60-100% of AFAB people with Danon disease will have abnormal electrical activity within the heart. Around one quarter will show a Wolff-Parkinson-White pattern on ECG testing.5 Possible symptoms and consequences of arrhythmias are as they are amongst AMAB patients, as discussed above. 

Other symptoms in AFAB patients

Muscle weakness occurs in 12-15% of AFAB patients but is typically not progressive, and CK enzyme levels are normal. Intellectual disability is not usually a feature. Around 20% will have retinal involvement. The impact on other organ systems is not well understood amongst AFAB patients.6

How is danon disease diagnosed?

A diagnosis of Danon disease is usually reached through a combination of medical history, examination, cardiac tests, and genetic testing.1

Firstly, your healthcare provider will take a detailed history of your or your child’s symptoms and development. They will consider the impact of any other health conditions or medications and establish whether other members of the family have similar features. An examination will look for signs of cardiac or neurological abnormalities. A neuropsychological assessment may be recommended if intellectual disability is suspected.1

An ECG will typically be carried out to look for abnormal electrical activity within the heart. An echocardiogram or cardiac MRI can detect structural abnormalities of the heart that we see in people with cardiomyopathy.1

Finally, your healthcare provider may take a blood test looking for changes in the LAMP2 gene that would support a diagnosis of Danon disease.1

If you or your child are showing symptoms of heart failure at diagnosis, additional blood tests and investigations may be required to guide onward management.1

What are the treatment options for danon's disease?

Treatment for Danon's disease usually involves managing the resulting cardiac features and the consequences of muscle weakness.1

Cardiac management

People with cardiomyopathy will require treatment to reduce the impact of this complication of Danon disease. Regular cardiac follow-up is recommended throughout a person’s life.5 Initially, medications may be used to help maximise heart function. However, further intervention is usually required as the degree of cardiomyopathy progresses, particularly in AMAB patients who should be considered for heart transplantation at an early stage.1 

The presence of cardiomyopathy increases the risk of arrhythmias, some of which can result in sudden cardiac death. An implantable cardiac defibrillator (ICD) should be considered for those with moderate to severe cardiomyopathy, who experience symptoms of arrhythmia, or who have a family history of sudden cardiac death.1 An ICD can deliver an electrical shock to the heart when it beats abnormally, helping to restore a normal rhythm. Some patients who experience symptoms of arrhythmias may be offered cardiac ablation, which uses radio waves or very cold temperatures to destroy abnormal electrical pathways within the heart. However, this is usually only a temporary solution for patients with Danon disease.1

Managing muscle weakness

Physical therapy can help manage muscle weakness. Regular light exercise may be recommended.1 An occupational therapist can also suggest any adaptations that could reduce the impact of the weakness on daily life. 

Other management considerations

Depending on individual symptoms, input from additional members of the healthcare team can be beneficial. If intellectual disability is present, then support should be provided to maximise quality of life and to support engagement in school, employment and daily activities. Regular eye tests are recommended, and for those with retinal involvement, referral to ophthalmology is typical. A genetic counsellor can help you to understand the risk of Danon disease for other members of your family.1

Resources for patients and families

Being diagnosed or having a child who is diagnosed with a rare genetic condition can be an isolating experience. Fortunately, there are many patient support organisations around the world.

If you do not see one listed that is relevant to your country, then speak to your healthcare team about locally available support: 

What is the outlook for people with danon disease?

The prognosis in Danon disease depends on the degree of cardiomyopathy.1 Unfortunately, AMAB patients are unlikely to survive beyond the age of 25 without a heart transplant. The mean age of heart transplantation is 17.2 years in AMAB patients and 33.7 years in AFAB patients. The mean age of death in AMAB patients is 19 years, and in AFAB patients, it is 34.6 years. It’s important to note that these are average ages, and many people live longer than this.9 


Danon disease is a rare, X-linked genetic condition that results from changes in the LAMP2 gene. Danon disease is an example of a lysosomal storage disease.

Symptoms are generally more severe in AMAB patients, who usually develop cardiomyopathy, muscle weakness and intellectual disability. The retinas, liver and respiratory system can also be affected in AMAB patients. Cardiac complications are the main feature in AFAB patients, although a minority will also experience skeletal muscle and retinal involvement. 

Diagnosis of Danon disease typically occurs through medical history and examination, cardiac tests like ECGs and echocardiograms, and genetic testing

Prognosis is linked to the severity of cardiomyopathy. Patients have a reduced life expectancy, particularly if they are AMAB. Medications, ICDs and cardiac transplantation can help reduce the impact of cardiomyopathy and other cardiac features, whilst input from physical and occupational therapists can help manage symptoms of muscle weakness. Regular eye tests are important, as are educational and social support for those with intellectual disabilities.

We understand that a diagnosis of Danon's disease can be a great shock for families. There are many patient support organisations around the world. In addition, a genetic counsellor can help you work through what the condition means for other members of your family who may be at risk. 


  1. D’Souza RS, Law L. Danon disease. In: StatPearls [Internet]. Treasure Island (FL): StatPearls Publishing; 2023 [cited 2023 Aug 14]. Available from: http://www.ncbi.nlm.nih.gov/books/NBK545211/ 
  2. Danon MJ, Oh SJ, DiMauro S, Manaligod JR, Eastwood A, Naidu S, et al. Lysosomal glycogen storage disease with normal acid maltase. Neurology [Internet]. 1981 Jan 1 [cited 2023 Aug 14];31(1):51–51. Available from: https://n.neurology.org/content/31/1/51 
  3. Rajkumar V, Dumpa V. Lysosomal storage disease. In: StatPearls [Internet]. Treasure Island (FL): StatPearls Publishing; 2023 [cited 2023 Aug 14]. Available from: http://www.ncbi.nlm.nih.gov/books/NBK563270/ 
  4. Pathak I, Bordoni B. Genetics, chromosomes. In: StatPearls [Internet]. Treasure Island (FL): StatPearls Publishing; 2023 [cited 2023 Aug 14]. Available from: http://www.ncbi.nlm.nih.gov/books/NBK557784/ 
  5. D’souza RS, Levandowski C, Slavov D, Graw SL, Allen LA, Adler E, et al. Danon disease: clinical features, evaluation, and management. Circ Heart Fail [Internet]. 2014 Sep [cited 2023 Aug 14];7(5):843–9. Available from: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4169002/ 
  6. Taylor MR, Adler ED. Danon disease. In: Adam MP, Mirzaa GM, Pagon RA, Wallace SE, Bean LJ, Gripp KW, et al., editors. GeneReviews® [Internet]. Seattle (WA): University of Washington, Seattle; 1993 [cited 2023 Aug 14]. Available from: http://www.ncbi.nlm.nih.gov/books/NBK554742/ 
  7. Brieler J, Breeden MA, Tucker J. Cardiomyopathy: an overview. AFP [Internet]. 2017 Nov 15 [cited 2023 Aug 14];96(10):640–6. Available from: https://www.aafp.org/pubs/afp/issues/2017/1115/p640.html
  8. Xu J, Li Z, Liu Y, Zhang X, Niu F, Zheng H, et al. Danon disease: a case report and literature review. Diagnostic Pathology [Internet]. 2021 May 1 [cited 2023 Aug 14];16(1):39. Available from: https://doi.org/10.1186/s13000-021-01100-8
  9. Boucek D, Jirikowic J, Taylor M. Natural history of Danon disease. Genet Med. 2011 Jun;13(6):563–8. 
This content is purely informational and isn’t medical guidance. It shouldn’t replace professional medical counsel. Always consult your physician regarding treatment risks and benefits. See our editorial standards for more details.

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Helen Maginnis

MBChB, BSc. (MedSci) Genetics, University of Glasgow

Helen is a former NHS doctor living in Scotland. She discovered her love for medical writing while working in the charity sector with families affected by Huntington’s disease. She has a special interest in rare genetic disorders and has conducted laboratory research examining the impact of collagen IV gene mutations in mice. Helen values diversity in all its forms and is a passionate LGBTQ+ rights advocate.

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