MCID: HYP366
MIFTS: 47

Hyperkalemic Periodic Paralysis, Type 2

Categories: Genetic diseases, Rare diseases, Metabolic diseases

Aliases & Classifications for Hyperkalemic Periodic Paralysis, Type 2

MalaCards integrated aliases for Hyperkalemic Periodic Paralysis, Type 2:

Name: Hyperkalemic Periodic Paralysis, Type 2 54 13
Hyperkalemic Periodic Paralysis 12 23 50 24 25 52 14 69
Gamstorp Disease 50 24 25 71
Familial Hyperkalemic Periodic Paralysis 12 25 29
Hyperpp 23 24 25
Adynamia Episodica Hereditaria with or Without Myotonia 50 71
Hyperkalemic Periodic Paralysis Type 2 24 69
Adynamia Episodica Hereditaria 24 25
Gamstorp Episodic Adynamy 50 25
Hypp 50 71
Familial Hyperkalemic Periodic Paralysis [ambiguous] 12
Primary Hyperkalemic Periodic Paralysis 25
Paralysis, Hyperkalemic Periodic 42
Periodic Paralysis Hyperkalemic 71
Periodic Paralysis Normokalemic 71
Periodic Hyperkalemic Paralysis 29
Sodium Channel Muscle Disease 50
Potassium Aggravated Myotonia 69
Periodic Paralysis Eukalemic 71
Hyperpp Type 2 24
Hyperkpp 25
Nkpp 71

Characteristics:

OMIM:

54
Inheritance:
autosomal dominant

Miscellaneous:
onset in infancy or early childhood
variable phenotype (myotonia may or may not be present)
acetazolamide is often effective
allelic disorder to paramyotonia congenita
allelic disorder to potassium-aggravated myotonia
allelic disorder to hypokalemic periodic paralysis (hokpp, )


HPO:

32
hyperkalemic periodic paralysis, type 2:
Onset and clinical course phenotypic variability infantile onset
Mortality/Aging death in infancy death in early adulthood
Inheritance autosomal dominant inheritance


GeneReviews:

23
Penetrance Usually, the penetrance is high (>90%). a few individuals with rare heterozygous pathogenic variants do not present with clinically detectable symptoms but have signs of myotonia detectable by emg only [mcclatchey et al 1992, wagner et al 1997]...

Classifications:



Summaries for Hyperkalemic Periodic Paralysis, Type 2

NIH Rare Diseases : 50 hyperkalemic periodic paralysis is a genetic disease that causes episodes of extreme muscle weakness and an increase of the potassium levels in the blood. muscle weakness during an attack usually affects the arms and legs and muscles of the eyes, throat, and trunk. most often, these episodes involve a temporary inability to move muscles in the arms and legs. episodes usually begin before age 20, usually between infancy and age 10. normally an episode lasts for 15 minutes to an hour, but in some people the episodes may last a few days to a week. episodes tend to increase in frequency until about age 50, after which they may occur less frequently. factors that can trigger attacks include rest after strenuous exercise, potassium-rich foods, stress, fatigue, and exposure to cold. depolarizing anesthetics should also be avoided. muscle strength usually returns to normal between episodes, although many people continue to experience mild stiffness, particularly in muscles of the face and hands. studies suggest more than 80% of people with hyperkalemic periodic paralysis over age 40 have permanent muscle weakness, most often affecting the leg muscles. about one third may develop a chronic progressive myopathy.  hyperkalemic periodic paralysis is caused by mutations in the scn4a gene and is inherited in an autosomal dominant manner. diagnosis is based on clinical symptoms including the increase of blood potassium level during an episode, but normal levels of blood potassium level in between episodes. genetic testing can confirm the diagnosis. treatment is focused on avoiding triggers and decreasing the severity of an episode. at the first sign of muscle weakness, episodes in many people may be prevented or stopped by mild exercise and/or eating carbohydrates, inhalation of salbutamol, or intravenous calcium gluconate. last updated: 8/18/2017

MalaCards based summary : Hyperkalemic Periodic Paralysis, Type 2, also known as hyperkalemic periodic paralysis, is related to hypokalemic periodic paralysis, type 1 and paramyotonia congenita, and has symptoms including hypertonia, hypokalemia and hyponatremia. An important gene associated with Hyperkalemic Periodic Paralysis, Type 2 is SCN4A (Sodium Voltage-Gated Channel Alpha Subunit 4), and among its related pathways/superpathways are Activation of cAMP-Dependent PKA and Cardiac conduction. The drugs Lamotrigine and Anticonvulsants have been mentioned in the context of this disorder. Affiliated tissues include testes, eye and skeletal muscle, and related phenotypes are homeostasis/metabolism and muscle

Genetics Home Reference : 25 Hyperkalemic periodic paralysis is a condition that causes episodes of extreme muscle weakness or paralysis, usually beginning in infancy or early childhood. Most often, these episodes involve a temporary inability to move muscles in the arms and legs. Episodes tend to increase in frequency until mid-adulthood, after which they occur less frequently. Factors that can trigger attacks include rest after exercise, potassium-rich foods such as bananas and potatoes, stress, fatigue, alcohol, pregnancy, exposure to cold temperatures, certain medications, and periods without food (fasting). Muscle strength usually returns to normal between attacks, although many affected people continue to experience mild stiffness (myotonia), particularly in muscles of the face and hands.

OMIM : 54
The 2 dominantly inherited, clinically similar types of episodic flaccid generalized weakness, HOKPP and HYPP, are distinguished by the changes in serum potassium levels during paralytic attacks. An important clinical difference between the 2 entities is represented by the triggers of attacks of weakness, e.g., HYPP can be provoked by oral potassium administration, whereas this is a remedy for HOKPP. Concurrence of myotonia is found in HYPP but usually not in HOKPP patients (Jurkat-Rott et al., 2000). Jurkatt-Rott and Lehmann-Horn (2007) provided a review of the clinical features, pathogenesis, and therapeutic options for HYPP. (170500)

UniProtKB/Swiss-Prot : 71 Periodic paralysis hyperkalemic: An autosomal dominant channelopathy characterized by episodic flaccid generalized muscle weakness associated with high levels of serum potassium. Concurrence of myotonia is found in HYPP patients. Periodic paralysis normokalemic: A disorder closely related to hyperkalemic periodic paralysis, but marked by a lack of alterations in potassium levels during attacks of muscle weakness.

Wikipedia : 72 Hyperkalemic periodic paralysis (HYPP, HyperKPP) is a genetic disorder. It occurs in humans, horses... more...

GeneReviews: NBK1496

Related Diseases for Hyperkalemic Periodic Paralysis, Type 2

Diseases in the Hyperkalemic Periodic Paralysis, Type 2 family:

Hyperkalemic Periodic Paralysis Type 1

Diseases related to Hyperkalemic Periodic Paralysis, Type 2 via text searches within MalaCards or GeneCards Suite gene sharing:

(show all 30)
id Related Disease Score Top Affiliating Genes
1 hypokalemic periodic paralysis, type 1 28.9 CACNA1S CLCN1 KCNE3 KCNJ2 SCN4A
2 paramyotonia congenita 28.8 CACNA1S CLCN1 KCNE3 KCNJ2 PTPRB SCN4A
3 hyperkalemic periodic paralysis type 1 12.4
4 myotonia congenita, atypical, acetazolamide-responsive 11.3
5 normokalemic periodic paralysis 11.1
6 amelogenesis imperfecta, hypomaturation type, iia6 10.3 CACNA1S SCN4A
7 chromosome 3q13.31 deletion syndrome 10.2 CLCN1 SCN4A
8 mitochondrial dna deletion syndromes 10.2 CACNA1S SCN4A
9 narcolepsy 10.2 CACNA1S SCN4A
10 central nervous system angiosarcoma 10.2 CLCN1 SCN4A
11 b cell deficiency 10.2 CLCN1 SCN4A
12 oropharynx cancer 10.1 CACNA1S SCN4A
13 myopathy 10.1
14 nevus cavernosus 10.0 CLCN1 SCN4A
15 tibial hemimelia cleft lip palate 10.0 CACNA1S KCNJ2
16 microvillus inclusion disease 9.9 KCNJ2 SCN4A
17 dysphagia 9.9
18 myotonia 9.9
19 tremor 9.9
20 bipolar disorder 9.9
21 myotonia congenita 9.9
22 pharyngitis 9.9
23 laryngitis 9.9
24 malignant hyperthermia 9.9
25 hyperphosphatemia 9.6 KCNE3 SCN4A
26 jervell and lange-nielsen syndrome 9.4 KCNE3 KCNJ2
27 vitelliform macular dystrophy 9.3 KCNE3 KCNJ2
28 hairy cell leukemia 9.1 KCNE3 KCNJ2
29 postinfectious encephalomyelitis 8.8 CACNA1S KCNE3 KCNJ2 SCN4A
30 monocular esotropia 7.8 CACNA1S CLCN1 KCNE3 KCNJ2 PTPRB SCN4A

Graphical network of the top 20 diseases related to Hyperkalemic Periodic Paralysis, Type 2:



Diseases related to Hyperkalemic Periodic Paralysis, Type 2

Symptoms & Phenotypes for Hyperkalemic Periodic Paralysis, Type 2

Symptoms via clinical synopsis from OMIM:

54

Muscle Soft Tissue:
flaccid weakness or paralysis, episodic attacks
muscle weakness is predominantly of extremities and tongue
attacks precipitated by rest after exercise
attacks precipitated by cold temperature
attacks precipitated by potassium
more
Laboratory- Abnormalities:
hyperkalemia during attacks


Clinical features from OMIM:

170500

Human phenotypes related to Hyperkalemic Periodic Paralysis, Type 2:

32 (show all 27)
id Description HPO Frequency HPO Source Accession
1 hypertonia 32 occasional (7.5%) HP:0001276
2 hypokalemia 32 occasional (7.5%) HP:0002900
3 hyponatremia 32 occasional (7.5%) HP:0002902
4 myopathy 32 occasional (7.5%) HP:0003198
5 myalgia 32 frequent (33%) HP:0003326
6 arrhythmia 32 occasional (7.5%) HP:0011675
7 congestive heart failure 32 occasional (7.5%) HP:0001635
8 respiratory insufficiency 32 occasional (7.5%) HP:0002093
9 hyperkalemia 32 frequent (33%) HP:0002153
10 feeding difficulties in infancy 32 occasional (7.5%) HP:0008872
11 ophthalmoparesis 32 occasional (7.5%) HP:0000597
12 malignant hyperthermia 32 occasional (7.5%) HP:0002047
13 cerebral palsy 32 hallmark (90%) HP:0100021
14 fasciculations 32 frequent (33%) HP:0002380
15 chest pain 32 occasional (7.5%) HP:0100749
16 gait disturbance 32 frequent (33%) HP:0001288
17 myotonia 32 frequent (33%) HP:0002486
18 paresthesia 32 occasional (7.5%) HP:0003401
19 bowel incontinence 32 occasional (7.5%) HP:0002607
20 flexion contracture 32 occasional (7.5%) HP:0001371
21 elevated serum creatine phosphokinase 32 hallmark (90%) HP:0003236
22 emg abnormality 32 hallmark (90%) HP:0003457
23 skeletal muscle atrophy 32 occasional (7.5%) HP:0003202
24 reduced tendon reflexes 32 hallmark (90%) HP:0001315
25 skeletal muscle hypertrophy 32 occasional (7.5%) HP:0003712
26 episodic flaccid weakness 32 hallmark (90%) HP:0003752
27 periodic hyperkalemic paralysis 32 hallmark (90%) HP:0007215

UMLS symptoms related to Hyperkalemic Periodic Paralysis, Type 2:


stridor, muscular stiffness, myalgia

MGI Mouse Phenotypes related to Hyperkalemic Periodic Paralysis, Type 2:

44
id Description MGI Source Accession Score Top Affiliating Genes
1 homeostasis/metabolism MP:0005376 9.63 CACNA1S CLCN1 KCNE3 KCNJ2 PTPRB SCN4A
2 muscle MP:0005369 9.35 CACNA1S CLCN1 KCNJ2 PTPRB SCN4A
3 respiratory system MP:0005388 8.8 KCNE3 KCNJ2 SCN4A

Drugs & Therapeutics for Hyperkalemic Periodic Paralysis, Type 2

Drugs for Hyperkalemic Periodic Paralysis, Type 2 (from DrugBank, HMDB, Dgidb, PharmGKB, IUPHAR, NovoSeek, BitterDB):

(show all 9)
id Name Status Phase Clinical Trials Cas Number PubChem Id
1
Lamotrigine Approved, Investigational Phase 3 84057-84-1 3878
2 Anticonvulsants Phase 3
3 calcium channel blockers Phase 3
4 Calcium, Dietary Phase 3
5 Diuretics, Potassium Sparing Phase 3
6 Excitatory Amino Acid Antagonists Phase 3
7 Excitatory Amino Acids Phase 3
8 Neurotransmitter Agents Phase 3
9 Sodium Channel Blockers Phase 3

Interventional clinical trials:


id Name Status NCT ID Phase Drugs
1 Lamotrigine as Treatment of Myotonia Completed NCT01939561 Phase 3 Lamotrigine;Placebo

Search NIH Clinical Center for Hyperkalemic Periodic Paralysis, Type 2

Cochrane evidence based reviews: paralysis, hyperkalemic periodic

Genetic Tests for Hyperkalemic Periodic Paralysis, Type 2

Genetic tests related to Hyperkalemic Periodic Paralysis, Type 2:

id Genetic test Affiliating Genes
1 Familial Hyperkalemic Periodic Paralysis 29
2 Periodic Hyperkalemic Paralysis 29
3 Hyperkalemic Periodic Paralysis 24
4 Hyperkalemic Periodic Paralysis Type 2 24

Anatomical Context for Hyperkalemic Periodic Paralysis, Type 2

MalaCards organs/tissues related to Hyperkalemic Periodic Paralysis, Type 2:

39
Testes, Eye, Skeletal Muscle, Heart, Tongue

Publications for Hyperkalemic Periodic Paralysis, Type 2

Variations for Hyperkalemic Periodic Paralysis, Type 2

UniProtKB/Swiss-Prot genetic disease variations for Hyperkalemic Periodic Paralysis, Type 2:

71
id Symbol AA change Variation ID SNP ID
1 SCN4A p.Thr704Met VAR_001562 rs80338957
2 SCN4A p.Ala1156Thr VAR_001565 rs80338958
3 SCN4A p.Leu1433Arg VAR_001571 rs121908550
4 SCN4A p.Met1592Val VAR_001575 rs80338962
5 SCN4A p.Arg675Gly VAR_037104 rs121908556
6 SCN4A p.Arg675Gln VAR_037105 rs121908557
7 SCN4A p.Arg675Trp VAR_037106 rs121908556
8 SCN4A p.Arg1129Gln VAR_064987 rs527236149

ClinVar genetic disease variations for Hyperkalemic Periodic Paralysis, Type 2:

6 (show all 21)
id Gene Variation Type Significance SNP ID Assembly Location
1 SCN4A NM_000334.4(SCN4A): c.2111C> T (p.Thr704Met) single nucleotide variant Pathogenic rs80338957 GRCh37 Chromosome 17, 62034787: 62034787
2 SCN4A NM_000334.4(SCN4A): c.4774A> G (p.Met1592Val) single nucleotide variant Pathogenic rs80338962 GRCh37 Chromosome 17, 62018868: 62018868
3 SCN4A NM_000334.4(SCN4A): c.4342C> T (p.Arg1448Cys) single nucleotide variant Pathogenic rs121908544 GRCh37 Chromosome 17, 62019300: 62019300
4 SCN4A NM_000334.4(SCN4A): c.4343G> A (p.Arg1448His) single nucleotide variant Pathogenic rs121908545 GRCh37 Chromosome 17, 62019299: 62019299
5 SCN4A NM_000334.4(SCN4A): c.3466G> A (p.Ala1156Thr) single nucleotide variant Pathogenic rs80338958 GRCh37 Chromosome 17, 62022974: 62022974
6 SCN4A NM_000334.4(SCN4A): c.2023C> T (p.Arg675Trp) single nucleotide variant Pathogenic rs121908556 GRCh37 Chromosome 17, 62034875: 62034875
7 SCN4A NM_000334.4(SCN4A): c.2006G> A (p.Arg669His) single nucleotide variant Pathogenic rs80338784 GRCh37 Chromosome 17, 62036638: 62036638
8 SCN4A NM_000334.4(SCN4A): c.2015G> A (p.Arg672His) single nucleotide variant Pathogenic rs80338788 GRCh37 Chromosome 17, 62036629: 62036629
9 SCN4A NM_000334.4(SCN4A): c.2014C> G (p.Arg672Gly) single nucleotide variant Pathogenic rs80338785 GRCh37 Chromosome 17, 62036630: 62036630
10 SCN4A NM_000334.4(SCN4A): c.2014C> A (p.Arg672Ser) single nucleotide variant Pathogenic rs80338785 GRCh37 Chromosome 17, 62036630: 62036630
11 SCN4A NM_000334.4(SCN4A): c.2023C> G (p.Arg675Gly) single nucleotide variant Pathogenic rs121908556 GRCh37 Chromosome 17, 62034875: 62034875
12 SCN4A NM_000334.4(SCN4A): c.2024G> A (p.Arg675Gln) single nucleotide variant Pathogenic rs121908557 GRCh37 Chromosome 17, 62034874: 62034874
13 SCN4A NM_000334.4(SCN4A): c.2078T> C (p.Ile693Thr) single nucleotide variant Pathogenic rs80338956 GRCh37 Chromosome 17, 62034820: 62034820
14 SCN4A NM_000334.4(SCN4A): c.2014C> T (p.Arg672Cys) single nucleotide variant Pathogenic rs80338785 GRCh37 Chromosome 17, 62036630: 62036630
15 SCN4A NM_000334.4(SCN4A): c.2065C> A (p.Leu689Ile) single nucleotide variant Pathogenic rs80338955 GRCh37 Chromosome 17, 62034833: 62034833
16 SCN4A NM_000334.4(SCN4A): c.4078A> G (p.Met1360Val) single nucleotide variant Pathogenic rs80338959 GRCh37 Chromosome 17, 62020396: 62020396
17 SCN4A NM_000334.4(SCN4A): c.4108A> G (p.Met1370Val) single nucleotide variant Pathogenic rs80338960 GRCh37 Chromosome 17, 62020366: 62020366
18 SCN4A NM_000334.4(SCN4A): c.4483A> T (p.Ile1495Phe) single nucleotide variant Pathogenic rs80338961 GRCh37 Chromosome 17, 62019159: 62019159
19 SCN4A NM_000334.4(SCN4A): c.4343G> C (p.Arg1448Pro) single nucleotide variant Pathogenic rs121908545 GRCh37 Chromosome 17, 62019299: 62019299
20 SCN4A NM_000334.4(SCN4A): c.4342C> A (p.Arg1448Ser) single nucleotide variant Pathogenic rs121908544 GRCh37 Chromosome 17, 62019300: 62019300
21 SCN4A NM_000334.4(SCN4A): c.1320T> G (p.Asn440Lys) single nucleotide variant Pathogenic rs864622785 GRCh37 Chromosome 17, 62041960: 62041960

Expression for Hyperkalemic Periodic Paralysis, Type 2

Search GEO for disease gene expression data for Hyperkalemic Periodic Paralysis, Type 2.

Pathways for Hyperkalemic Periodic Paralysis, Type 2

GO Terms for Hyperkalemic Periodic Paralysis, Type 2

Cellular components related to Hyperkalemic Periodic Paralysis, Type 2 according to GeneCards Suite gene sharing:

id Name GO ID Score Top Affiliating Genes
1 integral component of membrane GO:0016021 9.73 CACNA1S CLCN1 KCNE3 KCNJ2 PTPRB SCN4A
2 integral component of plasma membrane GO:0005887 9.46 CLCN1 KCNJ2 PTPRB SCN4A
3 plasma membrane GO:0005886 9.43 CACNA1S CLCN1 KCNE3 KCNJ2 PTPRB SCN4A
4 voltage-gated potassium channel complex GO:0008076 9.32 KCNE3 KCNJ2
5 sarcolemma GO:0042383 9.07 CLCN1
6 T-tubule GO:0030315 8.62 CACNA1S KCNJ2

Biological processes related to Hyperkalemic Periodic Paralysis, Type 2 according to GeneCards Suite gene sharing:

id Name GO ID Score Top Affiliating Genes
1 transport GO:0006810 9.65 CACNA1S CLCN1 KCNE3 KCNJ2 SCN4A
2 transmembrane transport GO:0055085 9.61 CACNA1S CLCN1 SCN4A
3 potassium ion transmembrane transport GO:0071805 9.48 KCNE3 KCNJ2
4 potassium ion transport GO:0006813 9.46 KCNE3 KCNJ2
5 cardiac conduction GO:0061337 9.4 CACNA1S KCNJ2
6 regulation of heart rate by cardiac conduction GO:0086091 9.37 KCNE3 KCNJ2
7 ion transport GO:0006811 9.35 CACNA1S CLCN1 KCNE3 KCNJ2 SCN4A
8 muscle contraction GO:0006936 9.33 CACNA1S CLCN1 SCN4A
9 membrane depolarization during action potential GO:0086010 9.32 CACNA1S SCN4A
10 regulation of ion transmembrane transport GO:0034765 9.02 CACNA1S CLCN1 KCNE3 KCNJ2 SCN4A

Molecular functions related to Hyperkalemic Periodic Paralysis, Type 2 according to GeneCards Suite gene sharing:

id Name GO ID Score Top Affiliating Genes
1 voltage-gated ion channel activity GO:0005244 8.92 CACNA1S CLCN1 KCNJ2 SCN4A

Sources for Hyperkalemic Periodic Paralysis, Type 2

3 CDC
7 CNVD
9 Cosmic
10 dbSNP
11 DGIdb
16 ExPASy
18 FMA
28 GO
29 GTR
30 HGMD
31 HMDB
32 HPO
33 ICD10
34 ICD10 via Orphanet
35 ICD9CM
36 IUPHAR
37 KEGG
38 LifeMap
40 MedGen
42 MeSH
43 MESH via Orphanet
44 MGI
46 NCI
47 NCIt
48 NDF-RT
51 NINDS
52 Novoseek
54 OMIM
55 OMIM via Orphanet
59 PubMed
60 QIAGEN
65 SNOMED-CT via HPO
66 SNOMED-CT via Orphanet
67 TGDB
68 Tocris
69 UMLS
70 UMLS via Orphanet
Content
Loading form....