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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

Patel U, Gunes E, Chawla A, Ashman K, Taub A, Arakelyan T, Madani A, Patel K, Bui Q, Adler E
Heart Fail Rev 2026 Jul 10;31(1) doi: 10.1007/s10741-026-10648-w. PMID: 42430006Free PMC Article
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
Ranganath PG, Tower-Rader A
Curr Cardiol Rep 2021 Jun 3;23(7):87. doi: 10.1007/s11886-021-01518-y. PMID: 34081227

Recent clinical studies

Etiology

Patel U, Gunes E, Chawla A, Ashman K, Taub A, Arakelyan T, Madani A, Patel K, Bui Q, Adler E
Heart Fail Rev 2026 Jul 10;31(1) doi: 10.1007/s10741-026-10648-w. PMID: 42430006Free PMC Article
Yin K, Li Y, Zhao H, Xu J, Yang H, Meng Y, Sun Y, Wang S, Zhou Z
Int J Cardiol Heart Vasc 2026 Aug;65:101958. Epub 2026 Jun 19 doi: 10.1016/j.ijcha.2026.101958. PMID: 42382315Free PMC Article
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
Shafiei S, Narimani Javid R, Haratian N, Moayedi Z, Aghakouchakzadeh M, Najafinezhad F, Azadnik S, Hoseini SM, Nozhat S, Laripour R, Ettehadi R, Zareei M, Ghanbari F, Ghassab MT, Ansarifahlyani G, Arzhangzade A
Curr Cardiol Rev 2026 Mar 11 doi: 10.2174/011573403X363296251202125302. PMID: 41830166
Liu N, Yang K, Cao G, Chen Z, Yin G, Dong W, Wang X, Li J, Lu M
J Magn Reson Imaging 2026 Feb;63(2):403-414. Epub 2025 Aug 30 doi: 10.1002/jmri.70102. PMID: 40884535

Diagnosis

Liu X, Liang S, Chen J, Chen Y
J Clin Med 2026 Aug 5;15(15) doi: 10.3390/jcm15156085. PMID: 42590185Free PMC Article
Patel U, Gunes E, Chawla A, Ashman K, Taub A, Arakelyan T, Madani A, Patel K, Bui Q, Adler E
Heart Fail Rev 2026 Jul 10;31(1) doi: 10.1007/s10741-026-10648-w. PMID: 42430006Free PMC Article
Yin K, Li Y, Zhao H, Xu J, Yang H, Meng Y, Sun Y, Wang S, Zhou Z
Int J Cardiol Heart Vasc 2026 Aug;65:101958. Epub 2026 Jun 19 doi: 10.1016/j.ijcha.2026.101958. PMID: 42382315Free PMC Article
Ribeiro GNP, Lipari LFVP, Senra PM, Pires LVL, Mizuta MH, Olivetti NQS, Aiello VD, Krieger JE
Arq Bras Cardiol 2026;123(3):e20250186. Epub 2026 May 15 doi: 10.36660/abc.20250186. PMID: 42154863Free PMC Article
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

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
Wang XY, Wang B, Zhu XL, Ma ZL, Liu Y, Lei CH, Yang QL, Hu D, Zhao XL, Liu ZR, Liu LW
Exp Ther Med 2021 Apr;21(4):395. Epub 2021 Feb 24 doi: 10.3892/etm.2021.9826. PMID: 33680117Free PMC Article
Lee JJ, Ishihara K, Notomi S, Efstathiou NE, Ueta T, Maidana D, Chen X, Iesato Y, Caligiana A, Vavvas DG
Biochem Biophys Res Commun 2020 Jan 8;521(2):414-419. Epub 2019 Oct 28 doi: 10.1016/j.bbrc.2019.10.138. PMID: 31672277Free PMC Article

Prognosis

Patel U, Gunes E, Chawla A, Ashman K, Taub A, Arakelyan T, Madani A, Patel K, Bui Q, Adler E
Heart Fail Rev 2026 Jul 10;31(1) doi: 10.1007/s10741-026-10648-w. PMID: 42430006Free PMC Article
Hu Y, Liu S, Liu Q, Liu B, Zhang J, Su H, Yang L, Gan L, Guo Y, He Y
Front Cardiovasc Med 2026;13:1695991. Epub 2026 May 7 doi: 10.3389/fcvm.2026.1695991. PMID: 42181643Free PMC Article
Zabłocki O, Bołkun A, Basaj A, Pietrzak R, Grabowski M, Ozierański K
Pol Arch Intern Med 2026 Jun 25;136(6) Epub 2026 May 12 doi: 10.20452/pamw.17302. PMID: 42138511
Arad M, Chaves AVF, Antunes M, Bakhsh A, Berger KI, Fat TH, Alves da Fonseca A, Furtado A, Maksimova I, Marques E Silva S, Maski M, Monjes E, Murillo Benitez NE, Ortuño Campos E, Ribeiro MG, Rodriguez-González MJ, Yu WC, Onay H
BMC Cardiovasc Disord 2026 Apr 17;26(1) doi: 10.1186/s12872-026-05834-5. PMID: 41998504Free PMC Article
Mannion J, Prendiville T, Murphy K, Galvin J
Acta Cardiol 2026 Apr;81(2):245-246. Epub 2026 Feb 10 doi: 10.1080/00015385.2026.2626613. PMID: 41668524

Clinical prediction guides

Yin K, Li Y, Zhao H, Xu J, Yang H, Meng Y, Sun Y, Wang S, Zhou Z
Int J Cardiol Heart Vasc 2026 Aug;65:101958. Epub 2026 Jun 19 doi: 10.1016/j.ijcha.2026.101958. PMID: 42382315Free PMC Article
Heath Jeffery RC, Kousal B, Grünert U, Curcio CA, Cherepanoff S, Lamey TM, Michaelides M, Tsika C, Chow I, Mahroo OA, Lee S, Meliska M, Kubanek M, Sikora J, Lin S, Wong RCB, Liskova P, Chen FK
Acta Ophthalmol 2026 Jun 28 doi: 10.1111/aos.70178. PMID: 42366573
Ribeiro GNP, Lipari LFVP, Senra PM, Pires LVL, Mizuta MH, Olivetti NQS, Aiello VD, Krieger JE
Arq Bras Cardiol 2026;123(3):e20250186. Epub 2026 May 15 doi: 10.36660/abc.20250186. PMID: 42154863Free PMC Article
Terni B, Quiles-Pastor M, Reynolds Z, Coppenrath K, Shaidani NI, Segundo PMS, Adam S, Riffo-Lepe N, Smith Z, Horb M, Aizenman C, Llobet A
bioRxiv 2026 Apr 15 doi: 10.64898/2026.04.14.718098. PMID: 42039380Free PMC Article
Arad M, Chaves AVF, Antunes M, Bakhsh A, Berger KI, Fat TH, Alves da Fonseca A, Furtado A, Maksimova I, Marques E Silva S, Maski M, Monjes E, Murillo Benitez NE, Ortuño Campos E, Ribeiro MG, Rodriguez-González MJ, Yu WC, Onay H
BMC Cardiovasc Disord 2026 Apr 17;26(1) doi: 10.1186/s12872-026-05834-5. PMID: 41998504Free PMC Article

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

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