Rare Nephrology News

Disease Profile

Danon disease

Prevalence
Prevalence estimates on Rare Medical Network websites are calculated based on data available from numerous sources, including US and European government statistics, the NIH, Orphanet, and published epidemiologic studies. Rare disease population data is recognized to be highly variable, and based on a wide variety of source data and methodologies, so the prevalence data on this site should be assumed to be estimated and cannot be considered to be absolutely correct.

<1 / 1 000 000

US Estimated

Europe Estimated

Age of onset

Childhood

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ICD-10

E74.0

Inheritance

Autosomal dominant A pathogenic variant in only one gene copy in each cell is sufficient to cause an autosomal dominant disease.

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Autosomal recessive Pathogenic variants in both copies of each gene of the chromosome are needed to cause an autosomal recessive disease and observe the mutant phenotype.

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X-linked
dominant X-linked dominant inheritance, sometimes referred to as X-linked dominance, is a mode of genetic inheritance by which a dominant gene is carried on the X chromosome.

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X-linked
recessive Pathogenic variants in both copies of a gene on the X chromosome cause an X-linked recessive disorder.

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Mitochondrial or multigenic Mitochondrial genetic disorders can be caused by changes (mutations) in either the mitochondrial DNA or nuclear DNA that lead to dysfunction of the mitochondria and inadequate production of energy.

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Multigenic or multifactor Inheritance involving many factors, of which at least one is genetic but none is of overwhelming importance, as in the causation of a disease by multiple genetic and environmental factors.

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Not applicable

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Other names (AKA)

Vacuolar cardiomyopathy and myopathy X-linked; X-linked vacuolar cardiomyopathy and myopathy; Antopol disease;

Categories

Congenital and Genetic Diseases; Heart Diseases; Metabolic disorders;

Summary

Danon disease is a rare genetic condition characterized by weakening of the heart muscle (cardiomyopathy), weakening of the muscles used for movement (skeletal muscles myopathy), and intellectual disability.[1][2] This condition is a type of lysosomal storage disorder.[3] Lysosomes are compartments within the cell that use enzymes to break down large molecules into smaller ones that the cell can use. In Danon disease there is a defect in the wall (membrane) of the lysosome. The defect is caused by variations (mutations) in the LAMP2 gene.[1][2][3] Danon disease is inherited in an X-linked dominant pattern. In this type of inheritance, males tend to be more severely affected than females and develop symptoms at a younger age.[1][2] Treatment is aimed at addressing the symptoms present in each individual and may require a team of specialists.[2]

Symptoms

The symptoms of Danon disease vary from case to case and depend on gender.[2] In general, the condition is characterized by cardiomyopathy, weakening of the skeletal muscles, and intellectual disability. Males usually develop the signs and symptoms of the condition earlier than females and are more severely affected. In males, the symptoms typically present in childhood or adolescence, while females may not have symptoms until early adulthood.[1][2]

Cardiomyopathy is the most common symptom of Danon disease and occurs in all males with the condition. Most (90%) affected men have hypertrophic cardiomyopathy, which causes the heart muscle to become thicker and more rigid than normal. A smaller number (10%) have dilated cardiomyopathy, which weakens and enlarges the heart. Both of these conditions affect the heart's ability to efficiently pump blood through the body and can cause serious complications, including heart failure and premature death. Many women with Danon disease also develop cardiomyopathy. Of these women, about half develop hypertrophic cardiomyopathy and the other half develop dilated cardiomyopathy.[1][2] 

People with Danon disease may also have other heart-related signs and symptoms, including a fluttering or pounding in the chest (palpitations), an abnormal heartbeat (arrhythmia), or chest pain. Many affected individuals also have abnormalities of the electrical signals that control the heartbeat (conduction abnormalities). The most common conduction abnormality seen in individuals with Danon disease is Wolff-Parkinson-White syndrome.[1][2]

Most men and about half of women with Danon disease also have skeletal myopathy. The muscles most often affected are those in the back, upper arms, shoulders, neck, and thighs. Many men also have elevated levels of an enzyme called creatine kinase (CPK) in their blood, which is an indicator of muscle disease.[1][2] 

Most men with Danon disease also have mild intellectual disability. In contrast, women tend to have normal intellectual development. Less common signs and symptoms may also be present, including gastrointestinal disease, breathing problems, and vision abnormalities.[1][2]

This table lists symptoms that people with this disease may have. For most diseases, symptoms will vary from person to person. People with the same disease may not have all the symptoms listed. This information comes from a database called the Human Phenotype Ontology (HPO) . The HPO collects information on symptoms that have been described in medical resources. The HPO is updated regularly. Use the HPO ID to access more in-depth information about a symptom.

Medical Terms Other Names
Learn More:
HPO ID
80%-99% of people have these symptoms
Cardiorespiratory arrest
0006543
Dilated cardiomyopathy
Stretched and thinned heart muscle
0001644
Gait disturbance
Abnormal gait
Abnormal walk
Impaired gait

[ more ]

 0001288
Hypertrophic cardiomyopathy
Enlarged and thickened heart muscle
0001639
Intellectual disability
Mental deficiency
Mental retardation
Mental retardation, nonspecific
Mental-retardation

[ more ]

 0001249
Muscle flaccidity
0010547
Percent of people who have these symptoms is not available through HPO
Arrhythmia
Abnormal heart rate
Heart rhythm disorders
Irregular heart beat
Irregular heartbeat

[ more ]

 0011675
Cardiomegaly
Enlarged heart
Increased heart size

[ more ]

 0001640
Cognitive impairment
Abnormality of cognition
Cognitive abnormality
Cognitive defects
Cognitive deficits
Intellectual impairment
Mental impairment

[ more ]

 0100543
Elevated serum creatine kinase
Elevated blood creatine phosphokinase
Elevated circulating creatine phosphokinase
Elevated creatine kinase
Elevated serum CPK
Elevated serum creatine phosphokinase
High serum creatine kinase
Increased CPK
Increased creatine kinase
Increased creatine phosphokinase
Increased serum CK
Increased serum creatine kinase
Increased serum creatine phosphokinase

[ more ]

 0003236
EMG: myopathic abnormalities
0003458
Exercise intolerance
Decreased ability to exercise
Inability to exercise

[ more ]

 0003546
Exercise-induced muscle cramps
Exercise-induced muscle cramping
Muscle cramps following exercise
Muscle cramps on exercise
Muscle cramps on exertion
Muscle cramps with exertion

[ more ]

 0003710
Generalized amyotrophy
Diffuse skeletal muscle wasting
Generalized muscle degeneration
Muscle atrophy, generalized

[ more ]

 0003700
Global developmental delay
0001263
Hypokinesia
Decreased muscle movement
Decreased spontaneous movement
Decreased spontaneous movements

[ more ]

 0002375
Myocardial fibrosis
0001685
Myocardial necrosis
0001700
Pes cavus
High-arched foot
0001761
Proximal muscle weakness
Weakness in muscles of upper arms and upper legs
0003701
Visual impairment
Impaired vision
Loss of eyesight
Poor vision

[ more ]

 0000505
Wolff-Parkinson-White syndrome
0001716
X-linked dominant inheritance
0001423
Do you have updated information on this disease? We want to hear from you.

Cause

Danon disease is caused by a variant (mutation) in the LAMP2 gene. LAMP2 stands for “lysosomal-associated membrane protein 2.”[3][4][5] Danon disease may also be caused by loss of genetic material (deletion) of the region of the chromosome X where the LAMP2 gene is located (Xq24).[6]

Diagnosis

Making a diagnosis for a genetic or rare disease can often be challenging. Healthcare professionals typically look at a person’s medical history, symptoms, physical exam, and laboratory test results in order to make a diagnosis. The following resources provide information relating to diagnosis and testing for this condition. If you have questions about getting a diagnosis, you should contact a healthcare professional.

Testing Resources

  • The Genetic Testing Registry (GTR) provides information about the genetic tests for this condition. The intended audience for the GTR is health care providers and researchers. Patients and consumers with specific questions about a genetic test should contact a health care provider or a genetics professional.
  • Orphanet lists international laboratories offering diagnostic testing for this condition.

    Newborn Screening

      Treatment

      Treatment is aimed at addressing the symptoms present in each individual. This may require a team of specialists in addition to the primary care physician, including a cardiologist, neurologist, ophthalmologist, geneticist, genetic counselor, rehabilitation physician, educational specialist, and physical therapist. Because Danon disease can be associated with rapidly progressive cardiomyopathy and sudden death, careful monitoring of heart disease is required. Medications for heart disease may be a first line of treatment. Aggressive interventions may be recommended for people showing signs of progressive heart failure (e.g., early intervention with heart transplantation or implantable cardioverter-defibrillator). Assessment of muscle strength should be performed regularly. Physical therapy may help maintain muscle strength and flexibility. Males with intellectual disabilities should receive appropriate educational interventions.[2]

      Organizations

      Support and advocacy groups can help you connect with other patients and families, and they can provide valuable services. Many develop patient-centered information and are the driving force behind research for better treatments and possible cures. They can direct you to research, resources, and services. Many organizations also have experts who serve as medical advisors or provide lists of doctors/clinics. Visit the group’s website or contact them to learn about the services they offer. Inclusion on this list is not an endorsement by GARD.

      Organizations Supporting this Disease

        Social Networking Websites

          Learn more

          These resources provide more information about this condition or associated symptoms. The in-depth resources contain medical and scientific language that may be hard to understand. You may want to review these resources with a medical professional.

          Where to Start

            In-Depth Information

            • Medscape Reference provides information on this topic. You may need to register to view the medical textbook, but registration is free.
            • The Monarch Initiative brings together data about this condition from humans and other species to help physicians and biomedical researchers. Monarch’s tools are designed to make it easier to compare the signs and symptoms (phenotypes) of different diseases and discover common features. This initiative is a collaboration between several academic institutions across the world and is funded by the National Institutes of Health. Visit the website to explore the biology of this condition.
            • Online Mendelian Inheritance in Man (OMIM) is a catalog of human genes and genetic disorders. Each entry has a summary of related medical articles. It is meant for health care professionals and researchers. OMIM is maintained by Johns Hopkins University School of Medicine. 
            • Orphanet is a European reference portal for information on rare diseases and orphan drugs. Access to this database is free of charge.
              Orphanet
              Orphanet
            • PubMed is a searchable database of medical literature and lists journal articles that discuss Danon disease. Click on the link to view a sample search on this topic.

              Selected Full-Text Journal Articles

                References

                1. Danon disease. Genetics Home Reference (GHR). March 2015; https://ghr.nlm.nih.gov/condition/danon-disease.
                2. Danon disease. National Organization for Rare Disorders (NORD). 2018; https://rarediseases.org/rare-diseases/danon-disease/.
                3. Danon disease. Online Mendelian Inheritance in Man. 2016; https://www.ncbi.nlm.nih.gov/entrez/dispomim.cgi?id=300257.
                4. Yang Z et al. Danon disease as an underrecognized cause of hypertrophic cardiomyopathy in children. Circulation. 2005;
                5. Maron BJ et al. Clinical outcome and phenotypic expression in LAMP2 cardiomyopathy. JAMA. 2009;
                6. Yang Z, Funke BH, Cripe LH, et al. LAMP2 microdeletions in patients with Danon disease. Circulation Cardiovascular genetics. 2010; 3(2):129-137. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2895413/.

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