MCID: DNN001
MIFTS: 48

Danon Disease

Categories: Genetic diseases, Rare diseases, Neuronal diseases, Metabolic diseases, Cardiovascular diseases

Aliases & Classifications for Danon Disease

MalaCards integrated aliases for Danon Disease:

Name: Danon Disease 54 12 50 24 25 56 71 29 13 52 14
Glycogen Storage Disease Type Iib 24 25 42 69
Vacuolar Cardiomyopathy and Myopathy X-Linked 50 71
X-Linked Vacuolar Cardiomyopathy and Myopathy 50 24
Glycogen Storage Disease Iib 24 71
Pseudoglycogenosis Ii 12 71
Antopol Disease 12 50
Gsd-Iib 24 71
Lysosomal Glycogen Storage Disease with Normal Acid Maltase Activity 56
Lysosomal Glycogen Storage Disease Without Acid Maltase Deficiency 71
Lysosomal Glycogen Storage Disease with Normal Acid Maltase 25
Glycogen Storage Disease Due to Lamp-2 Deficiency 56
Glycogen Storage Disease Limited to the Heart 50
Glycogenosis Due to Lamp-2 Deficiency 56
Glycogen Storage Disease Type 2b 25
Glycogen Storage Cardiomyopathy 50
Gsd Due to Lamp-2 Deficiency 56
Pseudoglycogenosis 2 50
Gsd2b 71
Dand 71

Characteristics:

Orphanet epidemiological data:

56
glycogen storage disease due to lamp-2 deficiency
Inheritance: X-linked recessive; Prevalence: <1/1000000 (Worldwide),<1/1000000 (Sweden); Age of onset: Childhood; Age of death: adult;

OMIM:

54
Miscellaneous:
phenotypic variability
not all patients have skeletal muscle symptoms or mental retardation
sudden death in affected males occurs in teens
sudden death in affected females occurs in the forties
females often show milder phenotype with later onset of cardiac symptoms

Inheritance:
x-linked dominant


HPO:

32
danon disease:
Onset and clinical course phenotypic variability
Inheritance x-linked dominant inheritance


Classifications:



Summaries for Danon Disease

OMIM : 54
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. (300257)

MalaCards based summary : Danon Disease, also known as glycogen storage disease type iib, is related to myopathy, x-linked, with excessive autophagy and cardiomyopathy, and has symptoms including visual impairment, cognitive impairment and cardiomegaly. An important gene associated with Danon Disease is LAMP2 (Lysosomal Associated Membrane Protein 2), and among its related pathways/superpathways is Lysosome. Affiliated tissues include skeletal muscle, heart and liver, and related phenotype is Decreased viability.

NIH Rare Diseases : 50 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. this condition is a type of lysosomal storage disorder.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 mutations in the lamp2 gene. danon disease is inherited in an x-linked dominant pattern. as a result, males tend to be more severely affected than females and develop symptoms at a younger age. treatment is aimed at addressing the symptoms present in each individual and may require a team of specialists.   last updated: 7/12/2016

UniProtKB/Swiss-Prot : 71 Danon disease: DAND is a lysosomal glycogen storage disease characterized by the clinical triad of cardiomyopathy, vacuolar myopathy and mental retardation. It is often associated with an accumulation of glycogen in muscle and lysosomes.

Genetics Home Reference : 25 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.

Wikipedia : 72 Danon disease (or glycogen storage disease Type IIb) is a metabolic disorder.Danon disease is an... more...

Related Diseases for Danon Disease

Graphical network of the top 20 diseases related to Danon Disease:



Diseases related to Danon Disease

Symptoms & Phenotypes for Danon Disease

Symptoms via clinical synopsis from OMIM:

54

Cardiovascular- Heart:
cardiomegaly
hypertrophic cardiomyopathy
dilated cardiomyopathy
arrhythmias
hypokinesia
more
Laboratory- Abnormalities:
increased serum creatine kinase

Head And Neck- Eyes:
moderate central loss of visual acuity in males (20/60)
normal to near-normal visual acuity in carrier females (20/30-20/20)
fine lamellar white opacities on slit lamp exam in carrier females
near complete loss of peripheral retinal pigment in males
peppered pigmentary mottling of peripheral retinal pigment in carrier females
more
Neurologic- Central Nervous System:
delayed development
cognitive impairment, mild
mental retardation (70%)

Muscle Soft Tissue:
exercise intolerance
emg shows myopathic changes
muscle cramps with exercise
severely decreased or absent lamp2 protein
proximal muscle weakness (85% of patients)
more
Skeletal- Feet:
pes cavus (uncommon)


Clinical features from OMIM:

300257

Human phenotypes related to Danon Disease:

32 (show all 19)
id Description HPO Frequency HPO Source Accession
1 visual impairment 32 HP:0000505
2 cognitive impairment 32 HP:0100543
3 cardiomegaly 32 HP:0001640
4 global developmental delay 32 HP:0001263
5 hypertrophic cardiomyopathy 32 HP:0001639
6 exercise intolerance 32 HP:0003546
7 dilated cardiomyopathy 32 HP:0001644
8 intellectual disability 32 very rare (1%) HP:0001249
9 pes cavus 32 HP:0001761
10 hypokinesia 32 HP:0002375
11 arrhythmia 32 HP:0011675
12 generalized amyotrophy 32 HP:0003700
13 proximal muscle weakness 32 HP:0003701
14 myocardial fibrosis 32 HP:0001685
15 myocardial necrosis 32 HP:0001700
16 wolff-parkinson-white syndrome 32 HP:0001716
17 elevated serum creatine phosphokinase 32 HP:0003236
18 exercise-induced muscle cramps 32 HP:0003710
19 emg 32 HP:0003458

GenomeRNAi Phenotypes related to Danon Disease according to GeneCards Suite gene sharing:

26
id Description GenomeRNAi Source Accession Score Top Affiliating Genes
1 Decreased viability GR00221-A-1 9.58 PIK3R4 PRKAG2 MPP2
2 Decreased viability GR00221-A-2 9.58 PIK3R4 PRKAG2 MPP2
3 Decreased viability GR00221-A-3 9.58 PIK3R4 MPP2
4 Decreased viability GR00221-A-4 9.58 PIK3R4

Drugs & Therapeutics for Danon Disease

Interventional clinical trials:


id Name Status NCT ID Phase Drugs
1 Remote Monitoring and Support for Patients With Schizophrenia, Schizoaffective or Bipolar Disorder on Adherence Not yet recruiting NCT02665611

Search NIH Clinical Center for Danon Disease

Cochrane evidence based reviews: glycogen storage disease type iib

Genetic Tests for Danon Disease

Genetic tests related to Danon Disease:

id Genetic test Affiliating Genes
1 Danon Disease 29 24 LAMP2

Anatomical Context for Danon Disease

MalaCards organs/tissues related to Danon Disease:

39
Skeletal Muscle, Heart, Liver, Skin, Brain

Publications for Danon Disease

Articles related to Danon Disease:

(show top 50) (show all 100)
id Title Authors Year
1
Danon disease for the cardiologist: case report and review of the literature. ( 28638575 )
2017
2
A Critical Evaluation of Liver Pathology in Humans with Danon Disease and Experimental Correlates in a Rat Model of LAMP-2 Deficiency. ( 28124283 )
2017
3
Autophagy dysregulation in Danon disease. ( 28102838 )
2017
4
Impaired mitophagy facilitates mitochondrial damage in Danon disease. ( 28526246 )
2017
5
Cardiac Danon disease: Insights and challenges. ( 28874294 )
2017
6
Neuropsychological functioning following cardiac transplant in Danon disease. ( 28594253 )
2017
7
Malignant cardiac phenotypic expression of Danon disease (LAMP2 cardiomyopathy). ( 28874292 )
2017
8
Heterogeneity in a large pedigree with Danon disease: Implications for pathogenesis and management. ( 28822614 )
2017
9
Psychiatric and cognitive characteristics of individuals with Danon disease (LAMP2 gene mutation). ( 28627787 )
2017
10
Identification of Two Novel LAMP2 Gene Mutations in Danon Disease. ( 27179547 )
2016
11
Amelioration of X-Linked Related Autophagy Failure in Danon Disease With DNA Methylation Inhibitor. ( 27678261 )
2016
12
Lymphoma in Danon disease with chronic rhabdomyolysis treated with EPOCH-R: A case report. ( 27442649 )
2016
13
Protein degradation in a LAMP-2-deficient B-lymphoblastoid cell line from a patient with Danon disease. ( 27130438 )
2016
14
Identification of LAMP2 Mutations in Early-Onset Danon Disease With Hypertrophic Cardiomyopathy by Targeted Next-Generation Sequencing. ( 27460667 )
2016
15
The c.65-2A>G splice site mutation is associated with a mild phenotype in Danon disease due to the transcription of normal LAMP2 mRNA. ( 26748608 )
2016
16
Early onset of cardiomyopathy and intellectual disability in a girl with Danon disease associated with a de novo novel mutation of the LAMP2 gene. ( 27145725 )
2016
17
Severe left ventricular hypertrophy and marked cardiac fibrosis in Danon disease. ( 27395820 )
2016
18
Cardiac arrhythmias in patients with Danon disease. ( 27742774 )
2016
19
A novel LAMP2 mutation associated with severe cardiac hypertrophy and microvascular remodeling in a female with Danon disease: a case report and literature review. ( 27497751 )
2016
20
Ischemic stroke due to hypoperfusion in a patient with a previously unrecognized Danon disease. ( 27816333 )
2016
21
Danon disease - dysregulation of autophagy in a multisystem disorder with cardiomyopathy. ( 27165304 )
2016
22
Hypertrophic Cardiomyopathy with Unusual Extensive Scarring Pattern: Danon Disease. ( 28289499 )
2016
23
LAMP-2 deficiency leads to hippocampal dysfunction but normal clearance of neuronal substrates of chaperone-mediated autophagy in a mouse model for Danon disease. ( 25637286 )
2015
24
THE PHYSIOLOGY OF THE RETINAL PIGMENT EPITHELIUM IN DANON DISEASE. ( 26398689 )
2015
25
Early onset cardiomyopathy in females with Danon disease. ( 25900304 )
2015
26
Oxidative Stress Mediates Cardiomyocyte Apoptosis in a Human Model of Danon Disease and Heart Failure. ( 25826782 )
2015
27
Danon disease: a phenotypic expression of LAMP-2 deficiency. ( 25589223 )
2015
28
Danon disease: a rare cause of left ventricular hypertrophy with cardiac magnetic resonance follow-up. ( 26206213 )
2015
29
LAMP2 flow cytometry in peripheral white blood cells is an established method that facilitates identification of heterozygous Danon disease female patients and mosaic mutation carriers. ( 25636828 )
2015
30
Danon disease and a new mutation of the LAMP-2 gene in a Spanish family. ( 26385016 )
2015
31
Asymptomatic young man with Danon disease. ( 24955057 )
2014
32
Mosaic tissue distribution of the tandem duplication of LAMP2 exons 4 and 5 demonstrates the limits of Danon disease cellular and molecular diagnostics. ( 23716275 )
2014
33
Early diagnosis of Danon disease: Flow cytometric detection of lysosome-associated membrane protein-2-negative leukocytes. ( 25458169 )
2014
34
Danon disease: clinical features, evaluation, and management. ( 25228319 )
2014
35
Novel LAMP2 mutations in Chinese patients with Danon disease cause varying degrees of clinical severity. ( 24691104 )
2014
36
Lysosomal storage and advanced senescence in the brain of LAMP-2-deficient Danon disease. ( 23262972 )
2013
37
Consider Danon disease in dilated cardiomyopathy with noncompaction. ( 23653338 )
2013
38
Danon disease : A novel mutation in the LAMP-2 gene and ophthalmic abnormality. ( 23955649 )
2013
39
Danon Disease Due to a Novel LAMP2 Microduplication. ( 24222494 )
2013
40
Late profound muscle weakness following heart transplantation due to Danon disease. ( 23168931 )
2013
41
Cystoid macular edema in a patient with Danon disease. ( 23571262 )
2013
42
Morphologic and clinical aspects of Danon disease in a patient with a mutation c.137G > A in the LAMP-2 gene. ( 23504560 )
2013
43
Danon disease: focusing on heart. ( 22695892 )
2012
44
A phenocopy of sarcomeric hypertrophic cardiomyopathy: LAMP2 cardiomyopathy (Danon disease) from China. ( 22187509 )
2012
45
Incremental value of three-dimensional strain imaging in Danon disease. ( 22581284 )
2012
46
Danon disease: a focus on processing of the novel LAMP2 mutation and comments on the beneficial use of peripheral white blood cells in the diagnosis of LAMP2 deficiency. ( 22365987 )
2012
47
Cone-rod dystrophy can be a manifestation of Danon disease. ( 22290069 )
2012
48
Sudden death associated with danon disease in women. ( 22074992 )
2012
49
Danon disease caused by two novel mutations of the LAMP2 gene: implications for two ends of the clinical spectrum. ( 22541782 )
2012
50
Danon disease as a cause of concentric left ventricular hypertrophy in patients who underwent endomyocardial biopsy. ( 22108829 )
2012

Variations for Danon Disease

UniProtKB/Swiss-Prot genetic disease variations for Danon Disease:

71
id Symbol AA change Variation ID SNP ID
1 LAMP2 p.Trp321Arg VAR_026230 rs104894859

ClinVar genetic disease variations for Danon Disease:

6 (show all 42)
id Gene Variation Type Significance SNP ID Assembly Location
1 LAMP2 LAMP2, 2-BP DEL, 1097AA deletion Pathogenic
2 LAMP2 NM_001122606.1(LAMP2): c.440T> A (p.Leu147Ter) single nucleotide variant Pathogenic rs137852527 GRCh37 Chromosome X, 119582941: 119582941
3 LAMP2 LAMP2, IVS6, G-C, +5 single nucleotide variant Pathogenic
4 LAMP2 LAMP2, 1-BP INS, 974A insertion Pathogenic
5 LAMP2 LAMP2, IVS5, G-A, +1 single nucleotide variant Pathogenic
6 LAMP2 LAMP2, 1-BP DEL, 14G deletion Pathogenic
7 LAMP2 LAMP2, 1-BP INS, 883T insertion Pathogenic
8 LAMP2 LAMP2, 7-BP DEL deletion Pathogenic
9 LAMP2 NM_001122606.1(LAMP2): c.520C> T (p.Gln174Ter) single nucleotide variant Pathogenic rs104894857 GRCh37 Chromosome X, 119582861: 119582861
10 LAMP2 NM_002294.2(LAMP2): c.928G> A (p.Val310Ile) single nucleotide variant Pathogenic rs104894858 GRCh37 Chromosome X, 119576454: 119576454
11 LAMP2 NM_001122606.1(LAMP2): c.961T> C (p.Trp321Arg) single nucleotide variant Pathogenic rs104894859 GRCh37 Chromosome X, 119575717: 119575717
12 LAMP2 LAMP2, 1-BP DEL, 1219A deletion Pathogenic
13 LAMP2 NM_002294.2(LAMP2): c.463delA (p.Ser155Valfs) deletion Likely pathogenic rs193922649 GRCh37 Chromosome X, 119582918: 119582918
14 LAMP2 NM_001122606.1(LAMP2): c.183T> A (p.Tyr61Ter) single nucleotide variant Likely pathogenic rs397516736 GRCh37 Chromosome X, 119590506: 119590506
15 LAMP2 NM_001122606.1(LAMP2): c.183T> G (p.Tyr61Ter) single nucleotide variant Likely pathogenic rs397516736 GRCh37 Chromosome X, 119590506: 119590506
16 LAMP2 NM_001122606.1(LAMP2): c.191delT (p.Val64Glufs) deletion Likely pathogenic rs397516738 GRCh37 Chromosome X, 119589418: 119589418
17 LAMP2 NM_002294.2(LAMP2): c.217_218insA (p.Thr73Asnfs) insertion Likely pathogenic rs397516739 GRCh37 Chromosome X, 119589392: 119589392
18 LAMP2 NM_002294.2(LAMP2): c.293G> A (p.Trp98Ter) single nucleotide variant Pathogenic rs397516740 GRCh37 Chromosome X, 119589316: 119589316
19 LAMP2 NM_002294.2(LAMP2): c.65-2A> G single nucleotide variant Pathogenic rs397516743 GRCh37 Chromosome X, 119590626: 119590626
20 LAMP2 NM_002294.2(LAMP2): c.864+3_864+6delGAGT deletion Pathogenic/Likely pathogenic rs397516751 GRCh37 Chromosome X, 119580154: 119580157
21 LAMP2 NM_002294.2(LAMP2): c.865-1G> C single nucleotide variant Likely pathogenic rs397516752 GRCh37 Chromosome X, 119576518: 119576518
22 LAMP2 NM_002294.2(LAMP2): c.1093+1G> A single nucleotide variant Pathogenic rs727504742 GRCh37 Chromosome X, 119575584: 119575584
23 LAMP2 NM_002294.2(LAMP2): c.999delA (p.Glu334Serfs) deletion Likely pathogenic rs727504557 GRCh38 Chromosome X, 120441824: 120441824
24 LAMP2 NM_002294.2(LAMP2): c.877C> T (p.Arg293Ter) single nucleotide variant Pathogenic rs727503118 GRCh37 Chromosome X, 119576505: 119576505
25 LAMP2 NM_002294.2(LAMP2): c.851_852delTT (p.Phe284Cysfs) deletion Pathogenic rs727504648 GRCh37 Chromosome X, 119580172: 119580173
26 LAMP2 NM_002294.2(LAMP2): c.183+1G> A single nucleotide variant Pathogenic/Likely pathogenic rs727503120 GRCh37 Chromosome X, 119590505: 119590505
27 LAMP2 NM_002294.2(LAMP2): c.1020delT (p.Gly341Glufs) deletion Pathogenic rs727504597 GRCh37 Chromosome X, 119575658: 119575658
28 LAMP2 NM_002294.2(LAMP2): c.929-1G> A single nucleotide variant Likely pathogenic rs727504262 GRCh37 Chromosome X, 119575750: 119575750
29 LAMP2 NM_002294.2(LAMP2): c.864+1G> T single nucleotide variant Pathogenic rs727503119 GRCh37 Chromosome X, 119580159: 119580159
30 LAMP2 NM_002294.2(LAMP2): c.121delT (p.Cys41Alafs) deletion Pathogenic rs727504600 GRCh37 Chromosome X, 119590568: 119590568
31 LAMP2 NC_000023.11: g.(?_120431323)_(120441894_?)del deletion Likely pathogenic GRCh37 Chromosome X, 119565178: 119575749
32 LAMP2 NM_002294.2(LAMP2): c.128_129dupAT (p.Ala44Metfs) duplication Likely pathogenic rs730880344 GRCh37 Chromosome X, 119590560: 119590561
33 LAMP2 NM_002294.2(LAMP2): c.795C> A (p.Cys265Ter) single nucleotide variant Pathogenic/Likely pathogenic rs730880483 GRCh37 Chromosome X, 119580229: 119580229
34 LAMP2 NM_002294.2(LAMP2): c.588_589insCAACA (p.Val197Glnfs) insertion Pathogenic rs730880492 GRCh38 Chromosome X, 120447993: 120447994
35 LAMP2 NM_002294.2(LAMP2): c.(?_398)-60_(741_?)+68del deletion Likely pathogenic GRCh38 Chromosome X, 120447773: 120449188
36 LAMP2 NM_002294.2(LAMP2): c.912T> G (p.Tyr304Ter) single nucleotide variant Likely pathogenic rs876657648 GRCh38 Chromosome X, 120442615: 120442615
37 LAMP2 NM_002294.2(LAMP2): c.294G> A (p.Trp98Ter) single nucleotide variant Pathogenic rs876657696 GRCh38 Chromosome X, 120455460: 120455460
38 LAMP2 NM_002294.2(LAMP2): c.962G> A (p.Trp321Ter) single nucleotide variant Pathogenic rs1060502306 GRCh38 Chromosome X, 120441861: 120441861
39 LAMP2 NM_002294.2(LAMP2): c.1013C> G (p.Ser338Ter) single nucleotide variant Pathogenic rs1060502305 GRCh38 Chromosome X, 120441810: 120441810
40 LAMP2 NM_002294.2(LAMP2): c.788delG (p.Gly263Alafs) deletion Pathogenic rs1060502303 GRCh38 Chromosome X, 120446381: 120446381
41 LAMP2 NM_001122606.1(LAMP2): c.546_548delGAGinsTA (p.Ser183Thrfs) indel Pathogenic rs1060502302 GRCh38 Chromosome X, 120448978: 120448980
42 LAMP2 NM_002294.2(LAMP2): c.973dupC (p.Leu325Profs) duplication Pathogenic GRCh38 Chromosome X, 120441850: 120441850

Expression for Danon Disease

Search GEO for disease gene expression data for Danon Disease.

Pathways for Danon Disease

Pathways related to Danon Disease according to GeneCards Suite gene sharing:

id Super pathways Score Top Affiliating Genes
1 10.71 GAA LAMP2

GO Terms for Danon Disease

Cellular components related to Danon Disease according to GeneCards Suite gene sharing:

id Name GO ID Score Top Affiliating Genes
1 endosome GO:0005768 9.61 LAMP2 PIK3R4 VPS4A
2 late endosome membrane GO:0031902 9.4 LAMP2 VPS4A
3 lysosomal lumen GO:0043202 9.37 GAA LAMP2
4 phagocytic vesicle membrane GO:0030670 9.32 LAMP2 PIK3R4
5 ficolin-1-rich granule membrane GO:0101003 9.26 GAA LAMP2
6 azurophil granule membrane GO:0035577 9.16 GAA LAMP2
7 late endosome GO:0005770 9.13 LAMP2 PIK3R4 VPS4A
8 lysosome GO:0005764 8.92 GAA LAMP2 VMA21 VPS4A

Biological processes related to Danon Disease according to GeneCards Suite gene sharing:

id Name GO ID Score Top Affiliating Genes
1 glycogen metabolic process GO:0005977 9.16 GAA PRKAG2
2 muscle cell cellular homeostasis GO:0046716 8.96 GAA LAMP2
3 macroautophagy GO:0016236 8.8 PIK3R4 PRKAG2 VPS4A

Sources for Danon Disease

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10 dbSNP
11 DGIdb
16 ExPASy
18 FMA
28 GO
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30 HGMD
31 HMDB
32 HPO
33 ICD10
34 ICD10 via Orphanet
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37 KEGG
38 LifeMap
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43 MESH via Orphanet
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65 SNOMED-CT via HPO
66 SNOMED-CT via Orphanet
67 TGDB
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70 UMLS via Orphanet
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