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Danon disease(GSD2B, FORMERLY)

MedGen UID:
209235
Concept ID:
C0878677
Disease or Syndrome
Synonyms: Antopol disease; Glycogen storage cardiomyopathy; Glycogen storage disease limited to the heart; Glycogen storage disease type 2b (formerly); Glycogen Storage Disease Type IIb; GSD IIb; GSD2B (formerly); LYSOSOMAL GLYCOGEN STORAGE DISEASE WITHOUT ACID MALTASE DEFICIENCY; Lysosomal glycogen storage disease without acid maltase deficiency (formerly); Pseudoglycogenosis 2; PSEUDOGLYCOGENOSIS II; Vacuolar cardiomyopathy and myopathy X-linked
Modes of inheritance:
X-linked recessive inheritance
MedGen UID:
375779
Concept ID:
C1845977
Finding
Sources: HPO, OMIM, 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.
X-linked dominant inheritance
MedGen UID:
376232
Concept ID:
C1847879
Finding
Sources: HPO, OMIM, Orphanet
A mode of inheritance that is observed for dominant traits related to a gene encoded on the X chromosome. In the context of medical genetics, X-linked dominant disorders tend to manifest very severely in affected males. The severity of manifestation in females may depend on the degree of skewed X inactivation.
X-linked recessive inheritance (HPO, OMIM, Orphanet)
X-linked dominant inheritance (HPO, OMIM, Orphanet)
SNOMED CT: Danon disease (419097006)
 
Gene (location): LAMP2 (Xq24)
OMIM®: 300257
Orphanet: ORPHA34587

Definition

Danon disease is an X-linked dominant disorder predominantly affecting cardiac muscle. Skeletal muscle involvement and mental retardation 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. [from OMIM]

Additional description

From GHR
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 disability. Males with Danon disease usually develop the condition earlier than females and are more severely affected. Signs and symptoms begin in childhood or adolescence in most affected males and in early adulthood in most affected females. Affected males, on average, live to age 19, while affected females live to an average age of 34.Cardiomyopathy is the most common symptom of Danon disease and occurs in all males with the condition. Most affected men have hypertrophic cardiomyopathy, which is a thickening of the heart muscle that may make it harder for the heart to pump blood. Other affected males have dilated cardiomyopathy, which is a condition that weakens and enlarges the heart, preventing it from pumping blood efficiently. Some affected men with hypertrophic cardiomyopathy later develop dilated cardiomyopathy. Either type of cardiomyopathy can lead to heart failure and premature death. Most women with Danon disease also develop cardiomyopathy; of the women who have this feature, about half have hypertrophic cardiomyopathy, and the other half have dilated cardiomyopathy.Affected individuals 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). People with Danon disease are often affected by 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 men with Danon disease and about half of affected women. The weakness typically occurs in the muscles of the upper arms, 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 men with Danon disease, but only a small percentage of affected women, have intellectual disability. If present, the disability is usually mild.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://ghr.nlm.nih.gov/condition/danon-disease

Clinical features

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.
Pes cavus
MedGen UID:
675590
Concept ID:
C0728829
Congenital Abnormality
The presence of an unusually high plantar arch. Also called high instep, pes cavus refers to a distinctly hollow form of the sole of the foot when it is bearing weight.
Primary dilated cardiomyopathy
MedGen UID:
2880
Concept ID:
C0007193
Disease or Syndrome
Nonsyndromic isolated dilated cardiomyopathy (DCM) is characterized by left ventricular enlargement and systolic dysfunction, a reduction in the myocardial force of contraction. DCM usually presents with any one of the following: Heart failure with symptoms of congestion (edema, orthopnea, paroxysmal nocturnal dyspnea) and/or reduced cardiac output (fatigue, dyspnea on exertion). Arrhythmias and/or conduction system disease. Thromboembolic disease (from left ventricular mural thrombus) including stroke.
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.
Wolff-Parkinson-White pattern
MedGen UID:
12162
Concept ID:
C0043202
Disease or Syndrome
Wolff-Parkinson-White syndrome is a condition characterized by abnormal electrical pathways in the heart that cause a disruption of the heart's normal rhythm (arrhythmia).The heartbeat is controlled by electrical signals that move through the heart in a highly coordinated way. A specialized cluster of cells called the atrioventricular node conducts electrical impulses from the heart's upper chambers (the atria) to the lower chambers (the ventricles). Impulses move through the atrioventricular node during each heartbeat, stimulating the ventricles to contract slightly later than the atria.People with Wolff-Parkinson-White syndrome are born with an extra connection in the heart, called an accessory pathway, that allows electrical signals to bypass the atrioventricular node and move from the atria to the ventricles faster than usual. The accessory pathway may also transmit electrical impulses abnormally from the ventricles back to the atria. This extra connection can disrupt the coordinated movement of electrical signals through the heart, leading to an abnormally fast heartbeat (tachycardia) and other changes in heart rhythm. Resulting symptoms include dizziness, a sensation of fluttering or pounding in the chest (palpitations), shortness of breath, and fainting (syncope). In rare cases, arrhythmias associated with Wolff-Parkinson-White syndrome can lead to cardiac arrest and sudden death. The most common arrhythmia associated with Wolff-Parkinson-White syndrome is called paroxysmal supraventricular tachycardia.Complications of Wolff-Parkinson-White syndrome can occur at any age, although some individuals born with an accessory pathway in the heart never experience any health problems associated with the condition.Wolff-Parkinson-White syndrome often occurs with other structural abnormalities of the heart or underlying heart disease. The most common heart defect associated with the condition is Ebstein anomaly, which affects the valve that allows blood to flow from the right atrium to the right ventricle (the tricuspid valve). Additionally, the heart rhythm problems associated with Wolff-Parkinson-White syndrome can be a component of several other genetic syndromes, including hypokalemic periodic paralysis (a condition that causes episodes of extreme muscle weakness), Pompe disease (a disorder characterized by the storage of excess glycogen), Danon disease (a condition that weakens the heart and skeletal muscles and causes intellectual disability), and tuberous sclerosis complex (a condition that results in the growth of noncancerous tumors in many parts of the body).
Myocardial fibrosis
MedGen UID:
56239
Concept ID:
C0151654
Pathologic Function
Myocardial necrosis
MedGen UID:
254841
Concept ID:
C1442837
Disease or Syndrome
ECG abnormality
MedGen UID:
321993
Concept ID:
C1832603
Finding
Any cardiac rhythm other than the normal sinus rhythm. Such a rhythm may be either of sinus or ectopic origin and either regular or irregular. An arrhythmia may be due to a disturbance in impulse formation or conduction or both.
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 delay
MedGen UID:
351243
Concept ID:
C1864897
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
Subnormal intellectual functioning which originates during the developmental period. This has multiple potential etiologies, including genetic defects and perinatal insults. Intelligence quotient (IQ) scores are commonly used to determine whether an individual has an intellectual disability. IQ scores between 70 and 79 are in the borderline range. Scores below 67 are in the disabled range. (from Joynt, Clinical Neurology, 1992, Ch55, p28)
Exercise intolerance
MedGen UID:
603270
Concept ID:
C0424551
Finding
A reduction in the ability to perform or withstand activities that induce physical or mental exertion.
Generalized amyotrophy
MedGen UID:
234650
Concept ID:
C1389113
Disease or Syndrome
Generalized (diffuse, unlocalized) amyotrophy (muscle atrophy) affecting multiple muscles.
Proximal muscle weakness
MedGen UID:
325534
Concept ID:
C1838869
Sign or Symptom
A lack of strength of the proximal 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.
Creatine phosphokinase, elevated serum
MedGen UID:
69128
Concept ID:
C0241005
Finding
The caveolinopathies, a group of muscle diseases, can be classified into five phenotypes, which can be seen in different members of the same family: Limb-girdle muscular dystrophy 1C (LGMD1C), characterized by onset usually in the first decade, mild-to-moderate proximal muscle weakness, calf hypertrophy, positive Gower sign, and variable muscle cramps after exercise . Isolated hyperCKemia (i.e., elevated serum concentration of creatine kinase (CK) in the absence of signs of muscle disease) (HCK). Rippling muscle disease (RMD), characterized by signs of increased muscle irritability, such as percussion-induced rapid contraction (PIRC), percussion-induced muscle mounding (PIMM), and/or electrically silent muscle contractions (rippling muscle). Distal myopathy (DM), observed in one individual only Hypertrophic cardiomyopathy (HCM), without skeletal muscle manifestations.

Term Hierarchy

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

Professional guidelines

PubMed

Authors/Task Force members., Elliott PM, Anastasakis A, Borger MA, Borggrefe M, Cecchi F, Charron P, Hagege AA, Lafont A, Limongelli G, Mahrholdt H, McKenna WJ, Mogensen J, Nihoyannopoulos P, Nistri S, Pieper PG, Pieske B, Rapezzi C, Rutten FH, Tillmanns C, Watkins H
Eur Heart J 2014 Oct 14;35(39):2733-79. Epub 2014 Aug 29 doi: 10.1093/eurheartj/ehu284. PMID: 25173338

Recent clinical studies

Etiology

Luo SS, Xi JY, Cai S, Zhao CB, Lu JH, Zhu WH, Lin J, Qiao K, Wang Y, Ye ZR
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Majer F, Pelak O, Kalina T, Vlaskova H, Dvorakova L, Honzik T, Palecek T, Kuchynka P, Masek M, Zeman J, Elleder M, Sikora J
J Inherit Metab Dis 2014 Jan;37(1):117-24. Epub 2013 May 29 doi: 10.1007/s10545-013-9617-z. PMID: 23716275
Van Der Starre P, Deuse T, Pritts C, Brun C, Vogel H, Oyer P
Muscle Nerve 2013 Jan;47(1):135-7. Epub 2012 Nov 21 doi: 10.1002/mus.23517. PMID: 23168931
Chen XL, Zhao Y, Ke HP, Liu WT, Du ZF, Zhang XN
Gene 2012 Oct 10;507(2):174-6. Epub 2012 Jun 30 doi: 10.1016/j.gene.2012.06.064. PMID: 22750798
Miani D, Taylor M, Mestroni L, D'Aurizio F, Finato N, Fanin M, Brigido S, Proclemer A
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Diagnosis

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Am J Cardiol 2016 Sep 15;118(6):888-94. Epub 2016 Jun 27 doi: 10.1016/j.amjcard.2016.06.037. PMID: 27460667
Sugie K, Yoshizawa H, Onoue K, Nakanishi Y, Eura N, Ogawa M, Nakano T, Sakaguchi Y, Hayashi YK, Kishimoto T, Shima M, Saito Y, Nishino I, Ueno S
Neuropathology 2016 Dec;36(6):561-565. Epub 2016 May 5 doi: 10.1111/neup.12307. PMID: 27145725
Hashida Y, Wada T, Saito T, Ohta K, Kasahara Y, Yachie A
J Cardiol 2015 Aug;66(2):168-74. Epub 2014 Nov 15 doi: 10.1016/j.jjcc.2014.09.011. PMID: 25458169
Luo SS, Xi JY, Cai S, Zhao CB, Lu JH, Zhu WH, Lin J, Qiao K, Wang Y, Ye ZR
Clin Neuropathol 2014 Jul-Aug;33(4):284-91. doi: 10.5414/NP300668. PMID: 24691104
Boucek D, Jirikowic J, Taylor M
Genet Med 2011 Jun;13(6):563-8. doi: 10.1097/GIM.0b013e31820ad795. PMID: 21415759

Therapy

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Circulation 2016 Nov 1;134(18):1373-1389. Epub 2016 Sep 27 doi: 10.1161/CIRCULATIONAHA.115.019847. PMID: 27678261
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Medicine (Baltimore) 2016 Jul;95(29):e4237. doi: 10.1097/MD.0000000000004237. PMID: 27442649Free PMC Article
Majer F, Pelak O, Kalina T, Vlaskova H, Dvorakova L, Honzik T, Palecek T, Kuchynka P, Masek M, Zeman J, Elleder M, Sikora J
J Inherit Metab Dis 2014 Jan;37(1):117-24. Epub 2013 May 29 doi: 10.1007/s10545-013-9617-z. PMID: 23716275
Van Der Starre P, Deuse T, Pritts C, Brun C, Vogel H, Oyer P
Muscle Nerve 2013 Jan;47(1):135-7. Epub 2012 Nov 21 doi: 10.1002/mus.23517. PMID: 23168931
Fanin M, Nascimbeni AC, Fulizio L, Spinazzi M, Melacini P, Angelini C
Am J Pathol 2006 Apr;168(4):1309-20. doi: 10.2353/ajpath.2006.050646. PMID: 16565504Free PMC Article

Prognosis

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Tex Heart Inst J 2014 Jun;41(3):332-4. Epub 2014 Jun 1 doi: 10.14503/THIJ-13-3279. PMID: 24955057Free PMC Article
Miani D, Taylor M, Mestroni L, D'Aurizio F, Finato N, Fanin M, Brigido S, Proclemer A
Am J Cardiol 2012 Feb 1;109(3):406-11. Epub 2011 Nov 9 doi: 10.1016/j.amjcard.2011.09.024. PMID: 22074992
Piotrowska-Kownacka D, Kownacki L, Kuch M, Walczak E, Kosieradzka A, Fidzianska A, Krolicki L
J Cardiovasc Magn Reson 2009 Apr 29;11:12. doi: 10.1186/1532-429X-11-12. PMID: 19402899Free PMC Article

Clinical prediction guides

Chanana AM, Rhee JW, Wu JC
Curr Opin Cardiol 2016 May;31(3):266-74. doi: 10.1097/HCO.0000000000000277. PMID: 27022891Free PMC Article
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Tex Heart Inst J 2014 Jun;41(3):332-4. Epub 2014 Jun 1 doi: 10.14503/THIJ-13-3279. PMID: 24955057Free PMC Article
Majer F, Pelak O, Kalina T, Vlaskova H, Dvorakova L, Honzik T, Palecek T, Kuchynka P, Masek M, Zeman J, Elleder M, Sikora J
J Inherit Metab Dis 2014 Jan;37(1):117-24. Epub 2013 May 29 doi: 10.1007/s10545-013-9617-z. PMID: 23716275
Majer F, Vlaskova H, Krol L, Kalina T, Kubanek M, Stolnaya L, Dvorakova L, Elleder M, Sikora J
Gene 2012 May 1;498(2):183-95. Epub 2012 Feb 21 doi: 10.1016/j.gene.2012.02.004. PMID: 22365987
Horváth J, Ketelsen UP, Geibel-Zehender A, Boehm N, Olbrich H, Korinthenberg R, Omran H
Neuropediatrics 2003 Jun;34(5):270-3. doi: 10.1055/s-2003-43262. PMID: 14598234

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