GSDH
MCID: GLY033
MIFTS: 33

Glycogen Storage Disease of Heart, Lethal Congenital (GSDH)

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

Aliases & Classifications for Glycogen Storage Disease of Heart, Lethal Congenital

MalaCards integrated aliases for Glycogen Storage Disease of Heart, Lethal Congenital:

Name: Glycogen Storage Disease of Heart, Lethal Congenital 57 29 13 6
Fatal Congenital Hypertrophic Cardiomyopathy Due to Glycogenosis 12 20 58
Fatal Congenital Hypertrophic Cardiomyopathy Due to Gsd 12 20 58
Phosphorylase Kinase Deficiency of Heart 57 12 72
Fatal Congenital Hypertrophic Cardiomyopathy Due to Glycogen Storage Disease 20 58
Lethal Congenital Glycogen Storage Disease of Heart 12 15
Glycogen Storage Disease of Heart 57 36
Storage Disease, Glycogen, Type of Heart, Lethal Congenital 39
Lethal Congenital Glycogen Storage Disease of the Heart 20
Glycogen Storage Disease of Heart Lethal Congenital 72
Fatal Congenital Nonlysosomal Cardiac Glycogenosis 12
Fatal Congenital Nonlysosomal Heart Glycogenosis 70
Congenital Nonlysosomal Cardiac Glycogenosis 72
Gsdh 72

Characteristics:

Orphanet epidemiological data:

58
fatal congenital hypertrophic cardiomyopathy due to glycogen storage disease
Inheritance: Not applicable; Prevalence: <1/1000000 (Worldwide); Age of onset: Antenatal,Neonatal; Age of death: infantile;

OMIM®:

57 (Updated 20-May-2021)
Inheritance:
autosomal dominant

Miscellaneous:
death in neonatal period


HPO:

31
glycogen storage disease of heart, lethal congenital:
Inheritance autosomal dominant inheritance


Classifications:

Orphanet: 58  
Inborn errors of metabolism


Summaries for Glycogen Storage Disease of Heart, Lethal Congenital

KEGG : 36 Glycogen storage disease of heart is an autosomal dominant disorder of glycogen metabolism. This disease is caused by mutations in the PRKAG2 gene, which encodes gamma-2 subunit of AMPK. It is characterized by fatal infantile cardiomyopathy, often associated with apparent phosphorylase b kinase deficiency.

MalaCards based summary : Glycogen Storage Disease of Heart, Lethal Congenital, also known as fatal congenital hypertrophic cardiomyopathy due to glycogenosis, is related to wolff-parkinson-white syndrome. An important gene associated with Glycogen Storage Disease of Heart, Lethal Congenital is PRKAG2 (Protein Kinase AMP-Activated Non-Catalytic Subunit Gamma 2), and among its related pathways/superpathways are AMPK signaling pathway and Insulin signaling pathway. Affiliated tissues include heart and kidney, and related phenotypes are macroglossia and abnormal facial shape

Disease Ontology : 12 A glycogen storage disease characterized by glycogenosis confined to the heart, hypoglycemia and cyanosis, and has material basis in autosomal dominant inheritance of heterozygous mutation in the gene encoding the noncatalytic gamma-2 subunit of AMP-activated protein kinase (PRKAG2) on chromosome 7q36.

UniProtKB/Swiss-Prot : 72 Glycogen storage disease of heart lethal congenital: Rare disease which leads to death within a few weeks to a few months after birth, through heart failure and respiratory compromise.

More information from OMIM: 261740

Related Diseases for Glycogen Storage Disease of Heart, Lethal Congenital

Diseases related to Glycogen Storage Disease of Heart, Lethal Congenital via text searches within MalaCards or GeneCards Suite gene sharing:

# Related Disease Score Top Affiliating Genes
1 wolff-parkinson-white syndrome 9.5 PRKAG2-AS1 PRKAG2

Symptoms & Phenotypes for Glycogen Storage Disease of Heart, Lethal Congenital

Human phenotypes related to Glycogen Storage Disease of Heart, Lethal Congenital:

31 (show all 15)
# Description HPO Frequency HPO Source Accession
1 macroglossia 31 occasional (7.5%) HP:0000158
2 abnormal facial shape 31 occasional (7.5%) HP:0001999
3 seizure 31 occasional (7.5%) HP:0001250
4 hypotension 31 HP:0002615
5 myopathy 31 HP:0003198
6 cardiomegaly 31 HP:0001640
7 congestive heart failure 31 HP:0001635
8 ascites 31 HP:0001541
9 neonatal hypoglycemia 31 HP:0001998
10 cardiomyopathy 31 HP:0001638
11 cyanosis 31 HP:0000961
12 pulmonary edema 31 HP:0100598
13 biventricular hypertrophy 31 HP:0200128
14 bradycardia 31 HP:0001662
15 shortened pr interval 31 HP:0005165

Symptoms via clinical synopsis from OMIM®:

57 (Updated 20-May-2021)
Cardiovascular Vascular:
hypotension

Abdomen External Features:
ascites

Respiratory Lung:
pulmonary edema
plural effusion

Head And Neck Mouth:
macroglossia (in some patients)

Muscle Soft Tissue:
vacuolar myopathy
atrophy, mild (in some cases)
increased glycogen in muscle (but to a lesser extent than in the heart)
normal phosphorylase kinase activity in muscle

Cardiovascular Heart:
cardiomegaly
congestive heart failure
biventricular hypertrophy
bradycardia, persistent, onset in utero
short pr interval
more
Metabolic Features:
neonatal hypoglycemia

Head And Neck Face:
dysmorphic facies, mild (in some patients)

Genitourinary Kidneys:
renomegaly

Neurologic Central Nervous System:
seizures (in 1 patient)

Clinical features from OMIM®:

261740 (Updated 20-May-2021)

Drugs & Therapeutics for Glycogen Storage Disease of Heart, Lethal Congenital

Search Clinical Trials , NIH Clinical Center for Glycogen Storage Disease of Heart, Lethal Congenital

Genetic Tests for Glycogen Storage Disease of Heart, Lethal Congenital

Genetic tests related to Glycogen Storage Disease of Heart, Lethal Congenital:

# Genetic test Affiliating Genes
1 Glycogen Storage Disease of Heart, Lethal Congenital 29 PRKAG2

Anatomical Context for Glycogen Storage Disease of Heart, Lethal Congenital

MalaCards organs/tissues related to Glycogen Storage Disease of Heart, Lethal Congenital:

40
Heart, Kidney

Publications for Glycogen Storage Disease of Heart, Lethal Congenital

Articles related to Glycogen Storage Disease of Heart, Lethal Congenital:

(show all 22)
# Title Authors PMID Year
1
Fatal infantile cardiac glycogenosis with phosphorylase kinase deficiency and a mutation in the gamma2-subunit of AMP-activated protein kinase. 57 6
17667862 2007
2
Fatal congenital heart glycogenosis caused by a recurrent activating R531Q mutation in the gamma 2-subunit of AMP-activated protein kinase (PRKAG2), not by phosphorylase kinase deficiency. 57 6
15877279 2005
3
Infantile hypertrophic cardiomyopathy of glycogenosis type IX: isolated cardiac phosphorylase kinase deficiency. 6 57
10368461 1999
4
Wolff-Parkinson-White Syndrome with Ventricular Hypertrophy in a Brazilian Family. 6
28690312 2017
5
Physiological Expression of AMPK╬│2RG Mutation Causes Wolff-Parkinson-White Syndrome and Induces Kidney Injury in Mice. 6
27621313 2016
6
Genome editing with CRISPR/Cas9 in postnatal mice corrects PRKAG2 cardiac syndrome. 6
27573176 2016
7
Results of clinical genetic testing of 2,912 probands with hypertrophic cardiomyopathy: expanded panels offer limited additional sensitivity. 6
25611685 2015
8
Using exome sequencing to identify the cause of myocardial hypertrophy in a Chinese family. 6
25997934 2015
9
PRKAG2 mutation: An easily missed cardiac specific non-lysosomal glycogenosis. 6
26085771 2015
10
Overexpression of G100S mutation in PRKAG2 causes Wolff-Parkinson-White syndrome in zebrafish. 6
23992123 2014
11
Distinct early signaling events resulting from the expression of the PRKAG2 R302Q mutant of AMPK contribute to increased myocardial glycogen. 6
20031621 2009
12
Shared genetic causes of cardiac hypertrophy in children and adults. 6
18403758 2008
13
Familial pseudo-Wolff-Parkinson-White syndrome. 6
16836667 2006
14
Transgenic mouse model of ventricular preexcitation and atrioventricular reentrant tachycardia induced by an AMP-activated protein kinase loss-of-function mutation responsible for Wolff-Parkinson-White syndrome. 6
15611370 2005
15
CBS domains form energy-sensing modules whose binding of adenosine ligands is disrupted by disease mutations. 6
14722619 2004
16
Fetal bradycardia at 28 weeks of gestation associated with cardiac glycogen phosphorylase b kinase deficiency. 6
14696860 2003
17
Novel PRKAG2 mutation responsible for the genetic syndrome of ventricular preexcitation and conduction system disease with childhood onset and absence of cardiac hypertrophy. 6
11748095 2001
18
Fatal infantile hypertrophic cardiomyopathy secondary to deficiency of heart specific phosphorylase b kinase. 57
8236826 1993
19
Fatal infantile cardiopathy caused by phosphorylase b kinase deficiency. 57
3385534 1988
20
Glycogen storage disease confined to the heart with deficient activity of cardiac phosphorylase kinase: a new type of glycogen storage disease. 57
3918928 1985
21
A new type of glycogen storage disease caused by deficiency of cardiac phosphorylase kinase. 57
6424667 1984
22
Novel PRKAG2 variant presenting as liver cirrhosis: report of a family with 2 cases and review of literature. 61
33509202 2021

Variations for Glycogen Storage Disease of Heart, Lethal Congenital

ClinVar genetic disease variations for Glycogen Storage Disease of Heart, Lethal Congenital:

6 (show top 50) (show all 260)
# Gene Name Type Significance ClinVarId dbSNP ID Position
1 PRKAG2 NM_016203.4(PRKAG2):c.1151G>C (p.Arg384Thr) SNV Pathogenic 183142 rs730882148 GRCh37: 7:151265884-151265884
GRCh38: 7:151568798-151568798
2 PRKAG2 NM_016203.4(PRKAG2):c.869A>T (p.Lys290Ile) SNV Pathogenic 943169 GRCh37: 7:151273534-151273534
GRCh38: 7:151576448-151576448
3 PRKAG2 NM_016203.4(PRKAG2):c.1588C>G (p.His530Asp) SNV Pathogenic 855977 GRCh37: 7:151257700-151257700
GRCh38: 7:151560614-151560614
4 PRKAG2 NM_016203.4(PRKAG2):c.905G>A (p.Arg302Gln) SNV Pathogenic 6846 rs121908987 GRCh37: 7:151273498-151273498
GRCh38: 7:151576412-151576412
5 PRKAG2 NM_016203.4(PRKAG2):c.1592G>T (p.Arg531Leu) SNV Pathogenic 45701 rs121908991 GRCh37: 7:151257696-151257696
GRCh38: 7:151560610-151560610
6 PRKAG2 NM_016203.4(PRKAG2):c.1589A>G (p.His530Arg) SNV Pathogenic 6854 rs267606977 GRCh37: 7:151257699-151257699
GRCh38: 7:151560613-151560613
7 PRKAG2 NM_016203.4(PRKAG2):c.1592G>A (p.Arg531Gln) SNV Pathogenic 6852 rs121908991 GRCh37: 7:151257696-151257696
GRCh38: 7:151560610-151560610
8 PRKAG2 NM_016203.4(PRKAG2):c.879C>A (p.Phe293Leu) SNV Likely pathogenic 36698 rs193922697 GRCh37: 7:151273524-151273524
GRCh38: 7:151576438-151576438
9 PRKAG2 NM_016203.4(PRKAG2):c.912G>A (p.Ala304=) SNV Conflicting interpretations of pathogenicity 45738 rs145029525 GRCh37: 7:151273491-151273491
GRCh38: 7:151576405-151576405
10 PRKAG2 NM_016203.4(PRKAG2):c.593C>T (p.Pro198Leu) SNV Uncertain significance 241096 rs41317142 GRCh37: 7:151372597-151372597
GRCh38: 7:151675511-151675511
11 PRKAG2 NM_016203.4(PRKAG2):c.1267C>A (p.Gln423Lys) SNV Uncertain significance 45693 rs147349145 GRCh37: 7:151262938-151262938
GRCh38: 7:151565852-151565852
12 PRKAG2 NM_016203.4(PRKAG2):c.202G>A (p.Gly68Ser) SNV Uncertain significance 181465 rs730880970 GRCh37: 7:151478502-151478502
GRCh38: 7:151781416-151781416
13 PRKAG2 NM_016203.4(PRKAG2):c.395A>G (p.Lys132Arg) SNV Uncertain significance 359347 rs779753891 GRCh37: 7:151478309-151478309
GRCh38: 7:151781223-151781223
14 PRKAG2 NM_016203.4(PRKAG2):c.131C>T (p.Ala44Val) SNV Uncertain significance 181483 rs730880984 GRCh37: 7:151483611-151483611
GRCh38: 7:151786525-151786525
15 PRKAG2 NM_016203.4(PRKAG2):c.425C>T (p.Thr142Ile) SNV Uncertain significance 45717 rs397517270 GRCh37: 7:151478279-151478279
GRCh38: 7:151781193-151781193
16 PRKAG2 NM_016203.4(PRKAG2):c.361A>G (p.Met121Val) SNV Uncertain significance 241095 rs760511236 GRCh37: 7:151478343-151478343
GRCh38: 7:151781257-151781257
17 PRKAG2 NM_016203.4(PRKAG2):c.704T>G (p.Leu235Arg) SNV Uncertain significance 410720 rs751094298 GRCh37: 7:151329205-151329205
GRCh38: 7:151632119-151632119
18 PRKAG2 NM_016203.4(PRKAG2):c.1687C>T (p.Gln563Ter) SNV Uncertain significance 45705 rs397517267 GRCh37: 7:151254310-151254310
GRCh38: 7:151557224-151557224
19 PRKAG2 NM_016203.4(PRKAG2):c.684C>T (p.Ala228=) SNV Uncertain significance 410719 rs151108625 GRCh37: 7:151372506-151372506
GRCh38: 7:151675420-151675420
20 PRKAG2 NM_016203.4(PRKAG2):c.455G>A (p.Arg152His) SNV Uncertain significance 410723 rs765374050 GRCh37: 7:151478249-151478249
GRCh38: 7:151781163-151781163
21 PRKAG2 NM_016203.4(PRKAG2):c.425C>T (p.Thr142Ile) SNV Uncertain significance 45717 rs397517270 GRCh37: 7:151478279-151478279
GRCh38: 7:151781193-151781193
22 PRKAG2 NM_016203.4(PRKAG2):c.1535A>T (p.Asn512Ile) SNV Uncertain significance 465340 rs766113743 GRCh37: 7:151261213-151261213
GRCh38: 7:151564127-151564127
23 PRKAG2 NM_016203.4(PRKAG2):c.554A>T (p.Glu185Val) SNV Uncertain significance 45724 rs397517274 GRCh37: 7:151372636-151372636
GRCh38: 7:151675550-151675550
24 PRKAG2 NM_016203.4(PRKAG2):c.1004T>C (p.Met335Thr) SNV Uncertain significance 181477 rs730880978 GRCh37: 7:151271978-151271978
GRCh38: 7:151574892-151574892
25 PRKAG2 NM_016203.4(PRKAG2):c.488C>T (p.Pro163Leu) SNV Uncertain significance 229172 rs876657963 GRCh37: 7:151372702-151372702
GRCh38: 7:151675616-151675616
26 PRKAG2 NM_016203.4(PRKAG2):c.685-6C>A SNV Uncertain significance 847650 GRCh37: 7:151329230-151329230
GRCh38: 7:151632144-151632144
27 PRKAG2 NM_016203.4(PRKAG2):c.32A>T (p.Lys11Ile) SNV Uncertain significance 410721 rs1060503025 GRCh37: 7:151573674-151573674
GRCh38: 7:151876589-151876589
28 PRKAG2 NC_000007.13:g.(?_151573582)_(151573715_?)dup Duplication Uncertain significance 657384 GRCh37: 7:151573582-151573715
GRCh38: 7:151876497-151876630
29 PRKAG2 NM_016203.4(PRKAG2):c.715G>A (p.Glu239Lys) SNV Uncertain significance 665806 rs1271179381 GRCh37: 7:151329194-151329194
GRCh38: 7:151632108-151632108
30 PRKAG2 NM_016203.4(PRKAG2):c.778_781dup (p.Tyr261fs) Duplication Uncertain significance 652121 rs1585114507 GRCh37: 7:151292513-151292514
GRCh38: 7:151595427-151595428
31 PRKAG2 NM_016203.4(PRKAG2):c.629A>G (p.Gln210Arg) SNV Uncertain significance 649514 rs1585679990 GRCh37: 7:151372561-151372561
GRCh38: 7:151675475-151675475
32 PRKAG2 NM_016203.4(PRKAG2):c.1466del (p.Asn489fs) Deletion Uncertain significance 639585 rs1584934953 GRCh37: 7:151261282-151261282
GRCh38: 7:151564196-151564196
33 PRKAG2 NM_016203.4(PRKAG2):c.1655A>G (p.Gln552Arg) SNV Uncertain significance 581064 rs1335765564 GRCh37: 7:151257633-151257633
GRCh38: 7:151560547-151560547
34 PRKAG2 NM_016203.4(PRKAG2):c.1663A>T (p.Ile555Phe) SNV Uncertain significance 572811 rs1563131128 GRCh37: 7:151257625-151257625
GRCh38: 7:151560539-151560539
35 PRKAG2 NM_016203.4(PRKAG2):c.43T>C (p.Ser15Pro) SNV Uncertain significance 572637 rs1563775284 GRCh37: 7:151573663-151573663
GRCh38: 7:151876578-151876578
36 PRKAG2 NM_016203.4(PRKAG2):c.1005+6T>C SNV Uncertain significance 533884 rs1554464077 GRCh37: 7:151271971-151271971
GRCh38: 7:151574885-151574885
37 PRKAG2 NM_016203.4(PRKAG2):c.467-2A>T SNV Uncertain significance 533880 rs1554531076 GRCh37: 7:151372725-151372725
GRCh38: 7:151675639-151675639
38 PRKAG2 NM_016203.4(PRKAG2):c.622T>A (p.Ser208Thr) SNV Uncertain significance 533879 rs1554530665 GRCh37: 7:151372568-151372568
GRCh38: 7:151675482-151675482
39 PRKAG2 NM_016203.4(PRKAG2):c.602G>A (p.Gly201Glu) SNV Uncertain significance 533877 rs1554530705 GRCh37: 7:151372588-151372588
GRCh38: 7:151675502-151675502
40 PRKAG2 NM_016203.4(PRKAG2):c.1049G>A (p.Arg350Lys) SNV Uncertain significance 533876 rs1330644534 GRCh37: 7:151269752-151269752
GRCh38: 7:151572666-151572666
41 PRKAG2 NM_016203.4(PRKAG2):c.56G>A (p.Gly19Glu) SNV Uncertain significance 533875 rs368522976 GRCh37: 7:151573650-151573650
GRCh38: 7:151876565-151876565
42 PRKAG2 NM_016203.4(PRKAG2):c.665A>G (p.His222Arg) SNV Uncertain significance 533874 rs1289045435 GRCh37: 7:151372525-151372525
GRCh38: 7:151675439-151675439
43 PRKAG2 NM_016203.4(PRKAG2):c.1060T>G (p.Leu354Val) SNV Uncertain significance 533873 rs1554459423 GRCh37: 7:151267303-151267303
GRCh38: 7:151570217-151570217
44 PRKAG2 NM_016203.4(PRKAG2):c.1198A>G (p.Thr400Ala) SNV Uncertain significance 533872 rs1554457901 GRCh37: 7:151265837-151265837
GRCh38: 7:151568751-151568751
45 PRKAG2 NM_016203.4(PRKAG2):c.1058A>G (p.Tyr353Cys) SNV Uncertain significance 465336 rs1554459431 GRCh37: 7:151267305-151267305
GRCh38: 7:151570219-151570219
46 PRKAG2 NM_016203.4(PRKAG2):c.1337T>G (p.Ile446Ser) SNV Uncertain significance 465339 rs1554455087 GRCh37: 7:151262868-151262868
GRCh38: 7:151565782-151565782
47 PRKAG2 NM_016203.4(PRKAG2):c.114G>C (p.Pro38=) SNV Uncertain significance 465338 rs397517261 GRCh37: 7:151573592-151573592
GRCh38: 7:151876507-151876507
48 PRKAG2 NM_016203.4(PRKAG2):c.978A>G (p.Ile326Met) SNV Uncertain significance 410717 rs1060503023 GRCh37: 7:151272004-151272004
GRCh38: 7:151574918-151574918
49 PRKAG2 NM_016203.4(PRKAG2):c.568C>A (p.Arg190Ser) SNV Uncertain significance 410722 rs202200501 GRCh37: 7:151372622-151372622
GRCh38: 7:151675536-151675536
50 PRKAG2 NM_016203.4(PRKAG2):c.1555A>G (p.Thr519Ala) SNV Uncertain significance 410718 rs1060503024 GRCh37: 7:151261193-151261193
GRCh38: 7:151564107-151564107

UniProtKB/Swiss-Prot genetic disease variations for Glycogen Storage Disease of Heart, Lethal Congenital:

72
# Symbol AA change Variation ID SNP ID
1 PRKAG2 p.Arg531Gln VAR_013269 rs121908991

Expression for Glycogen Storage Disease of Heart, Lethal Congenital

Search GEO for disease gene expression data for Glycogen Storage Disease of Heart, Lethal Congenital.

Pathways for Glycogen Storage Disease of Heart, Lethal Congenital

Pathways related to Glycogen Storage Disease of Heart, Lethal Congenital according to KEGG:

36
# Name Kegg Source Accession
1 AMPK signaling pathway hsa04152
2 Insulin signaling pathway hsa04910
3 Glucagon signaling pathway hsa04922

GO Terms for Glycogen Storage Disease of Heart, Lethal Congenital

Sources for Glycogen Storage Disease of Heart, Lethal Congenital

3 CDC
7 CNVD
9 Cosmic
10 dbSNP
11 DGIdb
17 EFO
18 ExPASy
19 FMA
20 GARD
28 GO
29 GTR
30 HMDB
31 HPO
32 ICD10
33 ICD10 via Orphanet
34 ICD9CM
35 IUPHAR
36 KEGG
37 LifeMap
39 LOVD
41 MedGen
44 MeSH
45 MESH via Orphanet
46 MGI
49 NCI
50 NCIt
51 NDF-RT
53 NINDS
54 Novoseek
56 OMIM via Orphanet
57 OMIM® (Updated 20-May-2021)
61 PubMed
63 QIAGEN
68 SNOMED-CT via HPO
69 Tocris
70 UMLS
71 UMLS via Orphanet
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