Glycogen storage disease due to LAMP-2 deficiency

General Information (adopted from Orphanet):

Synonyms, Signs: PSEUDOGLYCOGENOSIS II
GSD2B, FORMERLY
VACUOLAR CARDIOMYOPATHY AND MYOPATHY, X-LINKED
LYSOSOMAL GLYCOGEN STORAGE DISEASE WITHOUT ACID MALTASE DEFICIENCY, FORMERLY
ANTOPOL DISEASE
Danon disease
GSD IIb, FORMERLY
Lysosomal glycogen storage disease with normal acid maltase activity
Glycogenosis due to LAMP-2 deficiency
GSD due to LAMP-2 deficiency
GLYCOGEN STORAGE DISEASE IIb
Number of Symptoms 53
OrphanetNr: 34587
OMIM Id: 300257
ICD-10: E74.0
UMLs:
MeSH:
MedDRA:
Snomed:

Prevalence, inheritance and age of onset:

Prevalence: No data available.
Inheritance: X-linked
X-linked dominant
- PMID: 25589223 [IBIS]
Age of onset: Childhood
- PMID: 25589223 [IBIS]

Disease classification (adopted from Orphanet):

Parent Diseases: Glycogen storage disease
 -Rare genetic disease
Glycogen storage disease with hypertrophic cardiomyopathy
 -Rare cardiac disease
 -Rare genetic disease
Lysosomal glycogen storage disease
 -Rare genetic disease
Muscular glycogenosis
 -Rare genetic disease
 -Rare neurologic disease
Syndromic neurometabolic disease with X-linked intellectual deficit
 -Rare genetic disease
 -Rare neurologic disease

Comment:

Women present with clinical symptoms and events approximately 15 years after men and report a higher proportion of cognitive and skeletal muscle problems than previously recognized (PMID:21415759). The average age for the onset of Danon disease symptoms was 12.1 ± 6.5 years in men and 28.1 ± 15 years in women (PMID:25589223).

Symptom Information: Sort by abundance 

1
 (HPO:0000505) Visual impairment 17296900 IBIS 297 / 7739
2
 (HPO:0007663) Reduced visual acuity 17296900 IBIS 100 / 7739
3
 (HPO:0007814) Retinal pigment epithelial mottling 17296900 IBIS 5 / 7739
4
 (HPO:0000512) Abnormal electroretinogram 17296900 IBIS 61 / 7739
5
 (HPO:0000548) Cone/cone-rod dystrophy 17296900 IBIS 47 / 7739
6
 (HPO:0007988) Macular hypopigmentation 17296900 IBIS 1 / 7739
7
 (HPO:0001263) Global developmental delay 21161685 IBIS 853 / 7739
8
 (HPO:0100543) Cognitive impairment Frequent [IBIS] 21415759 IBIS 230 / 7739
9
 (HPO:0001249) Intellectual disability Frequent [IBIS] 21415759 IBIS 1089 / 7739
10
 (HPO:0100749) Chest pain 21415759 IBIS 92 / 7739
11
 (HPO:0001761) Pes cavus 15505188 IBIS 225 / 7739
12
 (HPO:0004309) Ventricular preexcitation 21415759 IBIS 6 / 7739
13
 (HPO:0001716) Wolff-Parkinson-White syndrome 21415759 IBIS 21 / 7739
14
 (HPO:0001712) Left ventricular hypertrophy 19318653 IBIS 76 / 7739
15
 (HPO:0001639) Hypertrophic cardiomyopathy Very frequent [IBIS] 25589223 IBIS 137 / 7739
16
 (HPO:0001700) Myocardial necrosis 15889279 IBIS 6 / 7739
17
 (HPO:0001695) Cardiac arrest 19318653 IBIS 87 / 7739
18
 (HPO:0001962) Palpitations 21415759 IBIS 62 / 7739
19
 (HPO:0011675) Arrhythmia 21415759 IBIS 226 / 7739
20
 (HPO:0001644) Dilated cardiomyopathy 21415759 IBIS 141 / 7739
21
 (HPO:0001638) Cardiomyopathy Very frequent [Orphanet] 25589223 IBIS 192 / 7739
22
 (HPO:0012664) Reduced ejection fraction 19318653 IBIS 32 / 7739
23
 (HPO:0001640) Cardiomegaly 19318653 IBIS 81 / 7739
24
 (HPO:0001685) Myocardial fibrosis 15889279 IBIS 30 / 7739
25
 (HPO:0000822) Hypertension 21415759 IBIS 224 / 7739
26
 (HPO:0006670) Impaired myocardial contractility 17849364 IBIS 9 / 7739
27
 (HPO:0004756) Ventricular tachycardia 21415759 IBIS 55 / 7739
28
 (HPO:0003236) Elevated serum creatine phosphokinase 21415759 IBIS 214 / 7739
29
 (HPO:0003077) Hyperlipidemia 21415759 IBIS 37 / 7739
30
 (HPO:0002093) Respiratory insufficiency 21415759 IBIS 410 / 7739
31
 (HPO:0001324) Muscle weakness Very frequent [Orphanet] 25589223 IBIS 859 / 7739
32
 (HPO:0003715) Myofibrillar myopathy 25589223 IBIS 9 / 7739
33
 (HPO:0003736) Autophagic vacuoles Very frequent [IBIS] 25589223 IBIS 5 / 7739
34
 (HPO:0003546) Exercise intolerance 21161685 IBIS 62 / 7739
35
 (HPO:0003710) Exercise-induced muscle cramps 21415759 IBIS 11 / 7739
36
 (HPO:0003202) Skeletal muscle atrophy 25589223 IBIS 281 / 7739
37
 (HPO:0003701) Proximal muscle weakness 25589223 IBIS 105 / 7739
38
 (HPO:0003458) EMG: myopathic abnormalities 16372318 IBIS 38 / 7739
39
 (OMIM) Cardiomyocytes show glycogen accumulation in myofibrils and lysosomes 25589223 IBIS 1 / 7739
40
 (OMIM) Positive staining for complement C5b-9 membrane attack complex proteins within vacuoles, but not on muscle fiber membrane 15792868 IBIS 1 / 7739
41
 (OMIM) Indentations or folds of the sarcolemma are connected to the membranes enclosing the vacuoles 25589223 IBIS 1 / 7739
42
 (OMIM) Near complete loss of peripheral retinal pigment in males 16751040 IBIS 1 / 7739
43
 (HPO:0030231) Glycogen accumulation in muscle fiber lysosomes 25589223 IBIS 1 / 7739
44
 (HPO:0011813) Increased cerebral lipofuscin 25589223 IBIS 4 / 7739
45
 (OMIM) Cardiomyocytes have irregular nuclei 15792868 IBIS 1 / 7739
46
 (OMIM) Severely decreased or absent LAMP2 protein 21415759 IBIS 1 / 7739
47
 (OMIM) Cardiomyocytes contain vacuolated cytoplasm with degenerated mitochondria, glycogen, and granular debris 15792868 IBIS 1 / 7739
48
 (OMIM) Vacuolar membranes immunostain with sarcolemmal proteins 25589223 IBIS 1 / 7739
49
 (OMIM) Muscle biopsy shows sarcoplasmic PAS-positive vacuoles 15253947 IBIS 1 / 7739
50
 (OMIM) Cognitive impairment, mild 21415759 IBIS 15 / 7739
51
 (HPO:0012758) Neurodevelopmental delay Very frequent [Orphanet] 25589223 IBIS 949 / 7739
52
 (OMIM) Normal alpha-glucosidase or acid maltase activity (GAA, 606800) 25589223 IBIS 3 / 7739
53
 (HPO:0003812) Phenotypic variability 21161685 IBIS 129 / 7739

Associated genes:

LAMP2;

ClinVar (via SNiPA)

Gene symbol Variation Clinical significance Reference
LAMP2 rs104894857 pathogenic RCV000010662.3
LAMP2 rs104894858 pathogenic RCV000010663.3
LAMP2 rs104894859 pathogenic RCV000010664.4
LAMP2 rs137852527 pathogenic RCV000010655.4
LAMP2 rs193922649 likely pathogenic RCV000037418.2
LAMP2 rs397516736 likely pathogenic RCV000037408.2
LAMP2 rs397516736 likely pathogenic RCV000037407.2
LAMP2 rs397516738 likely pathogenic RCV000037410.2
LAMP2 rs397516739 likely pathogenic RCV000037411.2
LAMP2 rs397516740 likely pathogenic RCV000037412.2
LAMP2 rs397516743 pathogenic RCV000037416.2
LAMP2 rs397516751 likely pathogenic RCV000037432.2
LAMP2 rs397516752 likely pathogenic RCV000037433.2
LAMP2 rs727503118 pathogenic RCV000150911.1
LAMP2 rs727503119 pathogenic RCV000150912.1
LAMP2 rs727503120 likely pathogenic RCV000150913.1
LAMP2 rs727504262 likely pathogenic RCV000154245.1
LAMP2 rs727504557 likely pathogenic RCV000155721.1
LAMP2 rs727504597 pathogenic RCV000155777.1
LAMP2 rs727504600 pathogenic RCV000155846.1
LAMP2 rs727504648 pathogenic RCV000155911.1
LAMP2 rs727504742 pathogenic RCV000156041.1
LAMP2 rs730880344 likely pathogenic RCV000154670.1

Additional Information:

Description: (OMIM) 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 ...
Clinical Description OMIM Antopol et al. (1940) described 2 brothers who died in the second decade of life with heart failure. Autopsy of 1 patient showed glycogen storage disease limited to the myocardium. Mehrizi and Oppenheimer (1960) reported 2 related patients ...
Genotype-Phenotype Correlations OMIM In a male patient with hypertrophic cardiomyopathy, exercise intolerance, and hyperCKemia consistent with a mild form of Danon disease, Musumeci et al. (2005) identified a missense mutation in the LAMP2 gene (309060.0011). The patient did not have muscle ...
Molecular genetics OMIM In 10 unrelated patients with Danon disease, Nishino et al. (2000) identified 10 different mutations in the LAMP2 gene (see, e.g., 309060.0001-309060.0006). All of the mutations resulted in premature termination of the LAMP2 protein. Several patients had previously ...