U.S. flag

An official website of the United States government

Format

Send to:

Choose Destination

Danon disease(GSD2B, FORMERLY)

MedGen UID:
209235
Concept ID:
C0878677
Disease or Syndrome
Synonyms: ANTOPOL DISEASE; Glycogen Storage Disease Type IIb; GSD IIb; LYSOSOMAL GLYCOGEN STORAGE DISEASE WITHOUT ACID MALTASE DEFICIENCY; PSEUDOGLYCOGENOSIS II
SNOMED CT: Danon disease (419097006); Glycogenosis due to LAMP-2 deficiency (419097006); Lysosomal glycogen storage disease with normal acid maltase activity (419097006); Glycogen storage disease due to LAMP-2 deficiency (419097006); Glycogen storage disease due to lysosomal associated membrane protein 2 deficiency (419097006)
Modes of inheritance:
X-linked recessive inheritance
MedGen UID:
375779
Concept ID:
C1845977
Finding
Source: Orphanet
A mode of inheritance that is observed for recessive traits related to a gene encoded on the X chromosome. In the context of medical genetics, X-linked recessive disorders manifest in males (who have one copy of the X chromosome and are thus hemizygotes), but generally not in female heterozygotes who have one mutant and one normal allele.
 
Gene (location): LAMP2 (Xq24)
 
Monarch Initiative: MONDO:0010281
OMIM®: 300257
Orphanet: ORPHA34587

Disease characteristics

Excerpted from the GeneReview: Danon Disease
Danon disease is a multisystem condition with predominant involvement of the heart, skeletal muscles, and retina, with overlying cognitive dysfunction. Males are typically more severely affected than females. Males usually present with childhood onset concentric hypertrophic cardiomyopathy that is progressive and often requires heart transplantation. Rarely, hypertrophic cardiomyopathy can evolve to resemble dilated cardiomyopathy. Most affected males also have cardiac conduction abnormalities. Skeletal muscle weakness may lead to delayed acquisition of motor milestones. Learning disability and intellectual disability, most often in the mild range, are common. Additionally, affected males can develop retinopathy with subsequent visual impairment. The clinical features in females are broader and more variable. Females are more likely to have dilated cardiomyopathy, with a smaller proportion requiring heart transplantation compared to affected males. Cardiac conduction abnormalities, skeletal muscle weakness, mild cognitive impairment, and pigmentary retinopathy are variably seen in affected females. [from GeneReviews]
Authors:
Matthew RG Taylor  |  Eric D Adler   view full author information

Additional descriptions

From OMIM
Danon disease is an X-linked dominant disorder predominantly affecting cardiac muscle. Skeletal muscle involvement and impaired intellectual development are variable features. The accumulation of glycogen in muscle and lysosomes originally led to the classification of Danon disease as a variant of glycogen storage disease II (Pompe disease; 232300) with 'normal acid maltase' or alpha-glucosidase (GAA; 606800) (Danon et al., 1981). However, Nishino et al. (2000) stated that Danon disease is not a glycogen storage disease because glycogen is not always increased. Sugie et al. (2005) classified Danon disease as a form of autophagic vacuolar myopathy, characterized by intracytoplasmic autophagic vacuoles with sarcolemmal features. The characteristic vacuole is believed to be an autolysosome surrounded by secondarily-generated membranes containing sarcolemmal proteins, basal lamina, and acetylcholinesterase activity. X-linked myopathy with excessive autophagy (XMEA; 310440) is a distinct disorder with similar pathologic features.  http://www.omim.org/entry/300257
From MedlinePlus Genetics
Danon disease is a condition characterized by weakening of the heart muscle (cardiomyopathy); weakening of the muscles used for movement, called skeletal muscles (myopathy); and intellectual disabilities. People with Danon disease may develop the condition at different ages. Signs and symptoms of this condition appear about 15 years earlier in males than in females. Males first experience health problems in childhood or adolescence; without treatment, these individuals typically live into early adulthood. Females start experiencing health problems in early adulthood and typically survive into mid-adulthood without treatment.

Cardiomyopathy is the most common symptom of Danon disease, and it occurs in all males and in most females. Beginning in childhood, most affected males develop hypertrophic cardiomyopathy, which is a thickening of the heart muscle that may make it harder for the heart to pump blood. Others with Danon disease may have dilated cardiomyopathy, which is a condition that weakens and enlarges the heart, preventing it from pumping blood efficiently. About half of females with Danon disease have hypertrophic cardiomyopathy, and the other half have dilated cardiomyopathy. Rarely, individuals with hypertrophic cardiomyopathy later develop dilated cardiomyopathy. Either type of cardiomyopathy can lead to heart failure and premature death.

Individuals with Danon disease can have other heart-related signs and symptoms, including a sensation of fluttering or pounding in the chest (palpitations), an abnormal heartbeat (arrhythmia), or chest pain. Many affected individuals have abnormalities of the electrical signals that control the heartbeat (conduction abnormalities). Affected individuals often have a specific conduction abnormality known as cardiac preexcitation. The type of cardiac preexcitation most often seen in people with Danon disease is called the Wolff-Parkinson-White syndrome pattern.

Skeletal myopathy occurs in most males with Danon disease and in some affected females. The weakness typically occurs in the muscles of the shoulders, neck, and upper thighs. Many males with Danon disease have elevated levels of an enzyme called creatine kinase in their blood, which often indicates muscle disease.

Most males with Danon disease have mild intellectual disabilities, but this is much less common in affected females.

There can be other signs and symptoms of the condition in addition to the three characteristic features. Several affected individuals have had gastrointestinal disease, breathing problems, or visual abnormalities.  https://medlineplus.gov/genetics/condition/danon-disease

Clinical features

From HPO
Exercise intolerance
MedGen UID:
603270
Concept ID:
C0424551
Finding
A functional motor deficit where individuals whose responses to the challenges of exercise fail to achieve levels considered normal for their age and gender.
Limb muscle weakness
MedGen UID:
107956
Concept ID:
C0587246
Finding
Reduced strength and weakness of the muscles of the arms and legs.
Pes cavus
MedGen UID:
675590
Concept ID:
C0728829
Congenital Abnormality
An increase in height of the medial longitudinal arch of the foot that does not flatten on weight bearing (i.e., a distinctly hollow form of the sole of the foot when it is bearing weight).
Atrioventricular block
MedGen UID:
13956
Concept ID:
C0004245
Disease or Syndrome
Delayed or lack of conduction of atrial depolarizations through the atrioventricular node to the ventricles.
Primary dilated cardiomyopathy
MedGen UID:
2880
Concept ID:
C0007193
Disease or Syndrome
Dilated cardiomyopathy is a form of heart disease in which the heart (cardiac) muscle becomes thin and enlarged (dilated). The dilation, which typically starts in the lower left chamber of the heart (left ventricle), makes it harder for the heart to pump blood to the rest of the body. \n\nDilated cardiomyopathy is called nonsyndromic dilated cardiomyopathy when it cannot be explained by other causes, such as a heart attack or damage to the valves of the heart, and is not associated with signs and symptoms that affect other parts of the body.  \n\nThe signs and symptoms of nonsyndromic dilated cardiomyopathy vary among affected individuals, even among members of the same family. The signs and symptoms typically begin in mid-adulthood, but they can occur at any time from infancy to late adulthood. Affected individuals may have a sensation of fluttering or pounding in the chest (palpitations); shortness of breath, especially when lying down or during physical activity; fatigue; and swelling of the legs and feet. Affected individuals may also have episodes of dizziness or fainting (syncope). \n\nOver time, people with nonsyndromic dilated cardiomyopathy may develop life-threatening complications, which can include abnormal heart rhythms (arrhythmias) and heart failure. Although uncommon, sudden death can occur in people with nonsyndromic dilated cardiomyopathy, even if they have no other symptoms of the condition.\n\n
Hypertrophic cardiomyopathy
MedGen UID:
2881
Concept ID:
C0007194
Disease or Syndrome
Hypertrophic cardiomyopathy (HCM) is defined by the presence of increased ventricular wall thickness or mass in the absence of loading conditions (hypertension, valve disease) sufficient to cause the observed abnormality.
Cardiomegaly
MedGen UID:
5459
Concept ID:
C0018800
Finding
Increased size of the heart, clinically defined as an increased transverse diameter of the cardiac silhouette that is greater than or equal to 50% of the transverse diameter of the chest (increased cardiothoracic ratio) on a posterior-anterior projection of a chest radiograph or a computed tomography.
Congestive heart failure
MedGen UID:
9169
Concept ID:
C0018802
Disease or Syndrome
The presence of an abnormality of cardiac function that is responsible for the failure of the heart to pump blood at a rate that is commensurate with the needs of the tissues or a state in which abnormally elevated filling pressures are required for the heart to do so. Heart failure is frequently related to a defect in myocardial contraction.
Syncope
MedGen UID:
21443
Concept ID:
C0039070
Sign or Symptom
A transient loss of consciousness (i.e., characterized by a rapid onset, a short duration, and a spontaneous and complete recovery) due to cerebral hypoperfusion.
Ventricular tachycardia
MedGen UID:
12068
Concept ID:
C0042514
Finding
A tachycardia originating in the ventricles characterized by rapid heart rate (over 100 beats per minute) and broad QRS complexes (over 120 ms).
Wolff-Parkinson-White pattern
MedGen UID:
12162
Concept ID:
C0043202
Disease or Syndrome
Wolff-Parkinson-White syndrome (WPW) is characterized by paroxysmal supraventricular tachycardia that may produce presyncope, syncope, and shortness of breath and cause sudden death. Electrocardiography shows a short PR interval with a widened QRS complex or an abnormal initial QRS vector (delta wave), diagnostic of ventricular preexcitation (summary by Gollob et al., 2001).
Atrial arrhythmia
MedGen UID:
39317
Concept ID:
C0085611
Pathologic Function
A type of supraventricular tachycardia in which the atria are the principal site of electrophysiologic disturbance.
Myocardial fibrosis
MedGen UID:
56239
Concept ID:
C0151654
Pathologic Function
Myocardial fibrosis is characterized by dysregulated collagen turnover (increased synthesis predominates over unchanged or decreased degradation) and excessive diffuse collagen accumulation in the interstitial and perivascular spaces as well as by phenotypically transformed fibroblasts, termed myofibroblasts.
Second degree atrioventricular block
MedGen UID:
75546
Concept ID:
C0264906
Disease or Syndrome
An intermittent atrioventricular block with failure of some atrial impulses to conduct to the ventricles, i.e., some but not all atrial impulses are conducted through the atrioventricular node and trigger ventricular contraction.
Increased QRS voltage
MedGen UID:
909971
Concept ID:
C1112650
Finding
Elevation of the voltage (height) of the QRS complex. There are several criteria in use, but the most common is the Sokolov-Lyon criterion (S wave depth in V1 + tallest R wave height in V5-V6 greater than 35 mm).
Myocardial necrosis
MedGen UID:
254841
Concept ID:
C1442837
Disease or Syndrome
Irreversible damage to heart tissue (myocardium) due to lack of oxygen after a heart attack (myocardial infarction).
Severely reduced left ventricular ejection fraction
MedGen UID:
868396
Concept ID:
C4022790
Finding
A large reduction in the fraction of blood pumped from the left ventricle with each cardiac cycle. The normal range in adults is at over 50 percent, and a severe reduction is defined as less than 30 percent.
Hypokinesia
MedGen UID:
39223
Concept ID:
C0086439
Finding
Abnormally diminished motor activity. In contrast to paralysis, hypokinesia is not characterized by a lack of motor strength, but rather by a poverty of movement. The typical habitual movements (e.g., folding the arms, crossing the legs) are reduced in frequency.
Cognitive impairment
MedGen UID:
90932
Concept ID:
C0338656
Mental or Behavioral Dysfunction
Abnormal cognition is characterized by deficits in thinking, reasoning, or remembering.
Global developmental delay
MedGen UID:
107838
Concept ID:
C0557874
Finding
A delay in the achievement of motor or mental milestones in the domains of development of a child, including motor skills, speech and language, cognitive skills, and social and emotional skills. This term should only be used to describe children younger than five years of age.
Intellectual disability
MedGen UID:
811461
Concept ID:
C3714756
Mental or Behavioral Dysfunction
The term intellectual disability or intellectual developmental disorder is used to describe significantly sub-average intellectual and adaptive functioning based on clinical assessment and as measured by individually administered, appropriately normed, standardized and validated tests of intellectual functioning and adaptive behavior, with onset during the developmental period from infancy through adolescence.
Muscle weakness
MedGen UID:
57735
Concept ID:
C0151786
Finding
Reduced strength of muscles.
Proximal muscle weakness
MedGen UID:
113169
Concept ID:
C0221629
Finding
A lack of strength of the proximal muscles.
Distal muscle weakness
MedGen UID:
140883
Concept ID:
C0427065
Finding
Reduced strength of the musculature of the distal extremities.
Generalized amyotrophy
MedGen UID:
234650
Concept ID:
C1389113
Disease or Syndrome
Generalized (diffuse, unlocalized) amyotrophy (muscle atrophy) affecting multiple muscles.
Exercise-induced muscle cramps
MedGen UID:
383715
Concept ID:
C1855578
Finding
Sudden and involuntary contractions of one or more muscles brought on by physical exertion.
EMG: myopathic abnormalities
MedGen UID:
867362
Concept ID:
C4021726
Pathologic Function
The presence of abnormal electromyographic patterns indicative of myopathy, such as small-short polyphasic motor unit potentials.
Lower limb amyotrophy
MedGen UID:
870475
Concept ID:
C4024921
Finding
Muscular atrophy affecting the lower limb.
Skeletal muscle autophagosome accumulation
MedGen UID:
1814214
Concept ID:
C5676640
Finding
Abnormal accumulation of autophagosomes in skeletal muscle tissue.
Elevated circulating creatine kinase activity
MedGen UID:
69128
Concept ID:
C0241005
Finding
The activity of creatine kinase in the blood circulation is above the upper limit of normal.
Visual impairment
MedGen UID:
777085
Concept ID:
C3665347
Finding
Visual impairment (or vision impairment) is vision loss (of a person) to such a degree as to qualify as an additional support need through a significant limitation of visual capability resulting from either disease, trauma, or congenital or degenerative conditions that cannot be corrected by conventional means, such as refractive correction, medication, or surgery.

Term Hierarchy

CClinical test,  RResearch test,  OOMIM,  GGeneReviews,  VClinVar  
Follow this link to review classifications for Danon disease in Orphanet.

Professional guidelines

PubMed

Ranganath PG, Tower-Rader A
Curr Cardiol Rep 2021 Jun 3;23(7):87. doi: 10.1007/s11886-021-01518-y. PMID: 34081227
Tanidir C, Tanidir IC, Tuzcu V
Cardiol Young 2015 Oct;25(7):1418-20. Epub 2014 Nov 17 doi: 10.1017/S1047951114002303. PMID: 25400066
D'souza RS, Levandowski C, Slavov D, Graw SL, Allen LA, Adler E, Mestroni L, Taylor MR
Circ Heart Fail 2014 Sep;7(5):843-9. doi: 10.1161/CIRCHEARTFAILURE.114.001105. PMID: 25228319Free PMC Article

Recent clinical studies

Etiology

Greenberg B, Taylor M, Adler E, Colan S, Ricks D, Yarabe P, Battiprolu P, Shah G, Patel K, Coggins M, Carou-Keenan S, Schwartz JD, Rossano JW
N Engl J Med 2025 Mar 6;392(10):972-983. Epub 2024 Nov 18 doi: 10.1056/NEJMoa2412392. PMID: 39556016
Argiro A, Bui Q, Hong KN, Ammirati E, Olivotto I, Adler E
JACC Heart Fail 2024 Feb;12(2):248-260. Epub 2023 Oct 7 doi: 10.1016/j.jchf.2023.09.015. PMID: 37966402
Fadl SA, Revels JW, Rezai Gharai L, Hanneman K, Dana F, Proffitt EK, Grizzard JD
Radiographics 2022 May-Jun;42(3):625-643. Epub 2022 Mar 11 doi: 10.1148/rg.210147. PMID: 35275782
Nishino I
Semin Pediatr Neurol 2006 Jun;13(2):90-5. doi: 10.1016/j.spen.2006.06.004. PMID: 17027858
Nishino I
Curr Neurol Neurosci Rep 2003 Jan;3(1):64-9. doi: 10.1007/s11910-003-0040-y. PMID: 12507414

Diagnosis

Maurizi N, Monda E, Biagini E, Field E, Passantino S, Dall' Aglio G, Fumagalli C, Antiochos P, Skalidis I, Pieroni M, Argirò A, Girolami F, Cecchi F, Barbey F, Monney P, Elliott PM, Kaski JP, Limongelli G, Olivotto I
Eur Heart J 2025 Aug 14;46(31):3082-3094. doi: 10.1093/eurheartj/ehaf026. PMID: 39928417
Greenberg B, Taylor M, Adler E, Colan S, Ricks D, Yarabe P, Battiprolu P, Shah G, Patel K, Coggins M, Carou-Keenan S, Schwartz JD, Rossano JW
N Engl J Med 2025 Mar 6;392(10):972-983. Epub 2024 Nov 18 doi: 10.1056/NEJMoa2412392. PMID: 39556016
Hong KN, Eshraghian EA, Arad M, Argirò A, Brambatti M, Bui Q, Caspi O, de Frutos F, Greenberg B, Ho CY, Kaski JP, Olivotto I, Taylor MRG, Yesso A, Garcia-Pavia P, Adler ED
J Am Coll Cardiol 2023 Oct 17;82(16):1628-1647. doi: 10.1016/j.jacc.2023.08.014. PMID: 37821174
Fadl SA, Revels JW, Rezai Gharai L, Hanneman K, Dana F, Proffitt EK, Grizzard JD
Radiographics 2022 May-Jun;42(3):625-643. Epub 2022 Mar 11 doi: 10.1148/rg.210147. PMID: 35275782
Sweet ME, Mestroni L, Taylor MRG
Heart Fail Clin 2018 Apr;14(2):215-224. doi: 10.1016/j.hfc.2017.12.003. PMID: 29525649Free PMC Article

Therapy

Greenberg B, Taylor M, Adler E, Colan S, Ricks D, Yarabe P, Battiprolu P, Shah G, Patel K, Coggins M, Carou-Keenan S, Schwartz JD, Rossano JW
N Engl J Med 2025 Mar 6;392(10):972-983. Epub 2024 Nov 18 doi: 10.1056/NEJMoa2412392. PMID: 39556016
Yadin D, Guetta T, Petrover Z, Alcalai R, Seidman J, Seidman CE, Ofek E, Kornowski R, Hochhauser E, Arad M
Biochem Pharmacol 2023 Sep;215:115735. Epub 2023 Aug 10 doi: 10.1016/j.bcp.2023.115735. PMID: 37572991
Zhai Y, Miao J, Peng Y, Wang Y, Dong J, Zhao X
Trends Cardiovasc Med 2023 Feb;33(2):81-89. Epub 2021 Nov 2 doi: 10.1016/j.tcm.2021.10.012. PMID: 34737089
Thakur R, Afzal A, Carey SA, Bass K, Felius J, Roberts WC, Hall SA
Rev Cardiovasc Med 2018 Jun 30;19(2):69-71. doi: 10.31083/j.rcm.2018.02.903. PMID: 31032605
Tanidir C, Tanidir IC, Tuzcu V
Cardiol Young 2015 Oct;25(7):1418-20. Epub 2014 Nov 17 doi: 10.1017/S1047951114002303. PMID: 25400066

Prognosis

Greenberg B, Taylor M, Adler E, Colan S, Ricks D, Yarabe P, Battiprolu P, Shah G, Patel K, Coggins M, Carou-Keenan S, Schwartz JD, Rossano JW
N Engl J Med 2025 Mar 6;392(10):972-983. Epub 2024 Nov 18 doi: 10.1056/NEJMoa2412392. PMID: 39556016
Sugie K, Nishino I
Biomolecules 2024 Oct 9;14(10) doi: 10.3390/biom14101272. PMID: 39456205Free PMC Article
Fadl SA, Revels JW, Rezai Gharai L, Hanneman K, Dana F, Proffitt EK, Grizzard JD
Radiographics 2022 May-Jun;42(3):625-643. Epub 2022 Mar 11 doi: 10.1148/rg.210147. PMID: 35275782
Cenacchi G, Papa V, Pegoraro V, Marozzo R, Fanin M, Angelini C
Neuropathol Appl Neurobiol 2020 Jun;46(4):303-322. Epub 2019 Nov 25 doi: 10.1111/nan.12587. PMID: 31698507
López-Sainz Á, Salazar-Mendiguchía J, García-Álvarez A, Campuzano Larrea O, López-Garrido MÁ, García-Guereta L, Fuentes Cañamero ME, Climent Payá V, Peña-Peña ML, Zorio-Grima E, Jordá-Burgos P, Díez-López C, Brugada R, García-Pinilla JM, García-Pavía P
Rev Esp Cardiol (Engl Ed) 2019 Jun;72(6):479-486. Epub 2018 Aug 11 doi: 10.1016/j.rec.2018.04.035. PMID: 30108015

Clinical prediction guides

Maurizi N, Monda E, Biagini E, Field E, Passantino S, Dall' Aglio G, Fumagalli C, Antiochos P, Skalidis I, Pieroni M, Argirò A, Girolami F, Cecchi F, Barbey F, Monney P, Elliott PM, Kaski JP, Limongelli G, Olivotto I
Eur Heart J 2025 Aug 14;46(31):3082-3094. doi: 10.1093/eurheartj/ehaf026. PMID: 39928417
Greenberg B, Taylor M, Adler E, Colan S, Ricks D, Yarabe P, Battiprolu P, Shah G, Patel K, Coggins M, Carou-Keenan S, Schwartz JD, Rossano JW
N Engl J Med 2025 Mar 6;392(10):972-983. Epub 2024 Nov 18 doi: 10.1056/NEJMoa2412392. PMID: 39556016
Argiro A, Bui Q, Hong KN, Ammirati E, Olivotto I, Adler E
JACC Heart Fail 2024 Feb;12(2):248-260. Epub 2023 Oct 7 doi: 10.1016/j.jchf.2023.09.015. PMID: 37966402
He J, Xu J, Chen L, Ji K, Fan X, Zhao S, Lu M
Clin Radiol 2020 Sep;75(9):712.e1-712.e11. Epub 2020 Jun 1 doi: 10.1016/j.crad.2020.04.012. PMID: 32499120
Nair V, Belanger EC, Veinot JP
Cardiovasc Pathol 2019 Mar-Apr;39:12-24. Epub 2018 Dec 1 doi: 10.1016/j.carpath.2018.11.002. PMID: 30594732

Recent systematic reviews

Emfietzoglou M, Sakuno G, Awh C, Hoyek S, Bantounou MA, Baroutis KG, Chatziralli I, Papaconstantinou D, Theodossiadis P, Charonis A, Patel NA, Vavvas DG
Am J Ophthalmol 2026 Jul;287:131-150. Epub 2026 Mar 25 doi: 10.1016/j.ajo.2026.03.026. PMID: 41895389
Brambatti M, Caspi O, Maolo A, Koshi E, Greenberg B, Taylor MRG, Adler ED
Int J Cardiol 2019 Jul 1;286:92-98. Epub 2019 Feb 16 doi: 10.1016/j.ijcard.2019.01.020. PMID: 30857840

Supplemental Content

Table of contents

    Clinical resources

    Practice guidelines

    • PubMed
      See practice and clinical guidelines in PubMed. The search results may include broader topics and may not capture all published guidelines. See the FAQ for details.
    • Bookshelf
      See practice and clinical guidelines in NCBI Bookshelf. The search results may include broader topics and may not capture all published guidelines. See the FAQ for details.

    Recent activity

    Your browsing activity is empty.

    Activity recording is turned off.

    Turn recording back on

    See more...