HOKPP1
MCID: HYP370
MIFTS: 51

Hypokalemic Periodic Paralysis, Type 1 (HOKPP1) malady

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

Aliases & Classifications for Hypokalemic Periodic Paralysis, Type 1

Aliases & Descriptions for Hypokalemic Periodic Paralysis, Type 1:

Name: Hypokalemic Periodic Paralysis, Type 1 54 13
Hypokalemic Periodic Paralysis 12 23 50 24 25 56 52 42 14 69
Hypopp 23 50 24 25 66
Hokpp 23 50 24 25 66
Westphall Disease 25 56 66
Familial Hypokalemic Periodic Paralysis 12 25
Hypokalemic Periodic Paralysis Type 1 24 69
Periodic Paralysis Hypokalemic 1 66 29
Periodic Hypokalemic Paralysis 12 29
Familial Periodic Paralysis 12 69
Hypokalemic Familial Periodic Paralysis 12
Primary Hypokalemic Periodic Paralysis 25
Periodic Paralysis I 12
Hypokpp 25
Hokpp1 66

Characteristics:

Orphanet epidemiological data:

56
hypokalemic periodic paralysis
Inheritance: Autosomal dominant; Prevalence: 1-9/100000 (Europe); Age of onset: Childhood; Age of death: normal life expectancy;

GeneReviews:

23
hypokalemic periodic paralysis, type 1:
Inheritance autosomal dominant inheritance
Onset and clinical course incomplete penetrance


GeneReviews:

23
Penetrance The penetrance of hokpp appears to depend on the specific pathogenic variant and the gender of the affected individual. in general, among individuals with pathogenic variants, females have fewer symptoms than males:...

Classifications:

Orphanet: 56  
Rare neurological diseases


External Ids:

OMIM 54 170400
Disease Ontology 12 DOID:14452
ICD10 33 G72.3
MeSH 42 D020514
NCIt 47 C84775
Orphanet 56 ORPHA681
MESH via Orphanet 43 D020514
UMLS via Orphanet 70 C0238358
ICD10 via Orphanet 34 G72.3
UMLS 69 C0238358

Summaries for Hypokalemic Periodic Paralysis, Type 1

NIH Rare Diseases : 50 hypokalemic periodic paralysis (hokpp) is a condition that causes episodes of muscle paralysis associated with a fall in blood potassium levels (hypokalemia). episodes typically involve a temporary inability to move muscles in the arms and legs. the first attack usually occurs in childhood or adolescence. attacks can last for hours or days, and the frequency of attacks varies among affected people. the frequency is usually highest between the ages of 15 and 35, and then decreases with age. some people with hokpp also develop late-onset proximal myopathy. hokpp can be caused by mutations in the cacna1s, scn4a, or kcnj18 gene. inheritance is autosomal dominant. treatment varies depending on the intensity and duration of attacks. minor attacks may resolve spontaneously, while treatment for moderate or severe attacks may involve ingesting oral potassium salts or intravenous potassium infusion. last updated: 10/4/2016

MalaCards based summary : Hypokalemic Periodic Paralysis, Type 1, also known as hypokalemic periodic paralysis, is related to hypokalemic periodic paralysis, type 2 and familial periodic paralysis, and has symptoms including emg abnormality, fatigable weakness of respiratory muscles and adrenocortical adenoma. An important gene associated with Hypokalemic Periodic Paralysis, Type 1 is CACNA1S (Calcium Voltage-Gated Channel Subunit Alpha1 S), and among its related pathways/superpathways are Vascular smooth muscle contraction and Circadian entrainment. The drugs Dichlorphenamide and Carbonic Anhydrase Inhibitors have been mentioned in the context of this disorder. Related phenotypes are behavior/neurological and growth/size/body region

Genetics Home Reference : 25 Hypokalemic periodic paralysis is a condition that causes episodes of extreme muscle weakness typically beginning in childhood or adolescence. Most often, these episodes involve a temporary inability to move muscles in the arms and legs. Attacks cause severe weakness or paralysis that usually lasts from hours to days. Some people may have episodes almost every day, while others experience them weekly, monthly, or only rarely. Attacks can occur without warning or can be triggered by factors such as rest after exercise, a viral illness, or certain medications. Often, a large, carbohydrate-rich meal or vigorous exercise in the evening can trigger an attack upon waking the following morning. Although affected individuals usually regain their muscle strength between attacks, repeated episodes can lead to persistent muscle weakness later in life.

OMIM : 54 There are 2 dominantly inherited, clinically similar types of episodic flaccid generalized weakness, HOKPP and HYPP,... (170400) more...

UniProtKB/Swiss-Prot : 66 Periodic paralysis hypokalemic 1: An autosomal dominant disorder manifested by episodic flaccid generalized muscle weakness associated with falls of serum potassium levels.

Wikipedia : 71 Hypokalemic periodic paralysis (hypoKPP) is a rare, autosomal dominant channelopathy characterized by... more...

GeneReviews: NBK1338

Related Diseases for Hypokalemic Periodic Paralysis, Type 1

Diseases in the Hypokalemic Periodic Paralysis, Type 1 family:

Hypokalemic Periodic Paralysis, Type 2

Diseases related to Hypokalemic Periodic Paralysis, Type 1 via text searches within MalaCards or GeneCards Suite gene sharing:

(show all 48)
id Related Disease Score Top Affiliating Genes
1 hypokalemic periodic paralysis, type 2 12.4
2 familial periodic paralysis 12.3
3 westphal disease 12.0
4 thyrotoxic periodic paralysis 1 11.7
5 thyrotoxic periodic paralysis 2 11.7
6 thyrotoxic periodic paralysis 11.5
7 hyperkalemic periodic paralysis, type 2 11.0
8 familial periodic paralyses 11.0
9 renal tubular acidosis 10.3
10 chromosome 3q13.31 deletion syndrome 10.3 CLCN1 SCN4A
11 primary pulmonary lymphoma 10.3 CACNA1S RYR1
12 heart block, progressive, type ia 10.2 CACNA1C KCNE3
13 oligodontia-colorectal cancer syndrome 10.2 QDPR SCN4A
14 paresthesia 10.2 CLCN1 SCN4A
15 multiminicore disease 10.2 CACNA1S RYR1 SCN4A
16 isolated encephalocele 10.2 CACNA1C KCNJ2
17 glaucoma 1, open angle, p 10.2 CACNA1S QDPR RYR1
18 hyperthyroidism 10.2
19 graves' disease 10.2
20 premature ovarian failure 5 10.2 CLCN1 RYR1 SCN4A
21 keppen-lubinsky syndrome 10.2 CACNA1C KCNJ2
22 b cell deficiency 10.1 CLCN1 RYR1 SCN4A
23 epilepsy, generalized, with febrile seizures plus, type 1 10.1 CACNA1S QDPR RYR1
24 pediatric angiosarcoma 10.1 CLCN1 RYR1 SCN4A
25 hypothyroidism, congenital, nongoitrous, 1 10.1 CACNA1S INS SCN4A
26 hyperthyroxinemia 10.1 CACNA1C KCNE3 KCNJ2
27 repetitive motion disorders 10.1 CACNA1S KCNE3 KCNJ2 SCN4A
28 myopathy 10.1
29 retinal cone dystrophy 4 10.1 CACNA1C TRDN
30 antley-bixler syndrome 10.1 CACNA1C KCNE3 SCN4A
31 cerebral creatine deficiency syndrome 10.1 CACNA1C KCNJ2 TRDN
32 soft palate cancer 10.1 CACNA1S QDPR RYR1 SCN4A
33 autosomal dominant nocturnal frontal lobe epilepsy 2 10.0 KCNJ2 RYR1 TRDN
34 segawa syndrome, recessive 10.0 QDPR RYR1 TRDN
35 ciliary dyskinesia, primary, 9, with or without situs inversus 10.0 CACNA1S KCNJ2 SCN4A TRDN
36 partial sensory epilepsy 10.0 ATP6V0A4 BRD4
37 ectopic cushing syndrome 9.9 ATP6V0A4 BRD4
38 rheumatic heart disease 9.9 TRDN XK
39 wolff-parkinson-white syndrome 9.9
40 photoparoxysmal response 3 9.8 INS XK
41 myotonia congenita, atypical, acetazolamide-responsive 9.7 CACNA1S CLCN1 KCNE3 KCNJ2 SCN4A XK
42 hypokalemia 9.6
43 waardenburg's syndrome 9.6
44 charcot-marie-tooth disease 9.6
45 tooth disease 9.6
46 atrial fibrillation, familial, 3 9.6 CACNA1C KCNE3 KCNE4 KCNJ2 TRDN XK
47 raynaud disease 9.4 ATP6V0A4 CACNA1S CLCN1 KCNE3 KCNJ2 QDPR
48 malignant hyperthermia susceptibility 5 8.2 ATP6V0A4 BRD4 CACNA1C CACNA1S CACNB4 CLCN1

Graphical network of the top 20 diseases related to Hypokalemic Periodic Paralysis, Type 1:



Diseases related to Hypokalemic Periodic Paralysis, Type 1

Symptoms & Phenotypes for Hypokalemic Periodic Paralysis, Type 1

Symptoms by clinical synopsis from OMIM:

170400

Clinical features from OMIM:

170400

Human phenotypes related to Hypokalemic Periodic Paralysis, Type 1:

56 32 (show all 19)
id Description HPO Frequency Orphanet Frequency HPO Source Accession
1 emg abnormality 56 32 Very frequent (99-80%) HP:0003457
2 fatigable weakness of respiratory muscles 56 32 Very rare (<4-1%) HP:0030196
3 adrenocortical adenoma 56 32 Very rare (<4-1%) HP:0008256
4 periodic hypokalemic paresis 56 32 Obligate (100%) HP:0008153
5 episodic hypokalemia 56 32 Obligate (100%) HP:0012726
6 episodic flaccid weakness 56 32 Very frequent (99-80%) HP:0003752
7 mildly elevated creatine phosphokinase 56 32 Very frequent (99-80%) HP:0008180
8 increased intramyocellular lipid droplets 56 32 Very frequent (99-80%) HP:0012240
9 exercise-induced muscle fatigue 56 32 Frequent (79-30%) HP:0009020
10 postprandial hyperglycemia 56 32 Frequent (79-30%) HP:0011998
11 late-onset proximal muscle weakness 56 32 Occasional (29-5%) HP:0003694
12 respiratory paralysis 56 32 Very rare (<4-1%) HP:0002203
13 hypokalemia 32 HP:0002900
14 myopathy 32 HP:0003198
15 myotonia 56 Excluded (0%)
16 paralysis 56 Very frequent (99-80%)
17 abnormality of muscle fibers 56 Very frequent (99-80%)
18 impaired myocardial contractility 56 Excluded (0%)
19 periodic hyperkalemic paralysis 32 HP:0007215

UMLS symptoms related to Hypokalemic Periodic Paralysis, Type 1:


muscle cramp, muscle rigidity, muscle spasticity, sciatica, muscle weakness, myalgia

MGI Mouse Phenotypes related to Hypokalemic Periodic Paralysis, Type 1:

44
id Description MGI Source Accession Score Top Affiliating Genes
1 behavior/neurological MP:0005386 10.09 ATP6V0A4 CACNA1C CACNA1S CACNB4 CLCN1 INS
2 growth/size/body region MP:0005378 10.02 ATP6V0A4 CACNA1S CACNB4 CLCN1 INS KCNJ2
3 homeostasis/metabolism MP:0005376 10 INS KCNE3 KCNJ2 QDPR RYR1 SCN4A
4 digestive/alimentary MP:0005381 9.88 CACNA1S CACNB4 INS KCNE3 KCNJ2 RYR1
5 mortality/aging MP:0010768 9.85 CACNA1C CACNA1S CACNB4 CLCN1 INS KCNJ2
6 hearing/vestibular/ear MP:0005377 9.72 ATP6V0A4 CACNB4 CLCN1 KCNE3 SCN4A
7 muscle MP:0005369 9.65 CACNA1C CACNA1S CACNB4 CLCN1 INS KCNJ2
8 skeleton MP:0005390 9.17 ATP6V0A4 CACNA1S CLCN1 INS KCNJ2 QDPR

Drugs & Therapeutics for Hypokalemic Periodic Paralysis, Type 1

Drugs for Hypokalemic Periodic Paralysis, Type 1 (from DrugBank, HMDB, Dgidb, PharmGKB, IUPHAR, NovoSeek, BitterDB):

(show all 7)
id Name Status Phase Clinical Trials Cas Number PubChem Id
1
Dichlorphenamide Approved Phase 3 120-97-8 3038
2 Carbonic Anhydrase Inhibitors Phase 3
3 Hops Nutraceutical Phase 3
4
Bumetanide Approved Phase 2 28395-03-1 2471
5 diuretics Phase 2
6 Natriuretic Agents Phase 2
7 Sodium Potassium Chloride Symporter Inhibitors Phase 2

Interventional clinical trials:


id Name Status NCT ID Phase
1 Hyper- and Hypokalemic Periodic Paralysis Study Completed NCT00494507 Phase 3
2 Phase III Randomized, Double-Blind, Placebo-Controlled Study of Dichlorphenamide for Periodic Paralyses and Associated Sodium Channel Disorders Completed NCT00004802 Phase 3
3 Bumetanide in Hypokalaemic Periodic Paralysis Active, not recruiting NCT02582476 Phase 2

Search NIH Clinical Center for Hypokalemic Periodic Paralysis, Type 1

Cochrane evidence based reviews: hypokalemic periodic paralysis

Genetic Tests for Hypokalemic Periodic Paralysis, Type 1

Genetic tests related to Hypokalemic Periodic Paralysis, Type 1:

id Genetic test Affiliating Genes
1 Hypokalemic Periodic Paralysis 29 24 SCN4A
2 Hypokalemic Periodic Paralysis 1 29
3 Hypokalemic Periodic Paralysis Type 1 24 CACNA1S

Anatomical Context for Hypokalemic Periodic Paralysis, Type 1

Publications for Hypokalemic Periodic Paralysis, Type 1

Variations for Hypokalemic Periodic Paralysis, Type 1

UniProtKB/Swiss-Prot genetic disease variations for Hypokalemic Periodic Paralysis, Type 1:

66
id Symbol AA change Variation ID SNP ID
1 CACNA1S p.Arg528His VAR_001499 rs80338777
2 CACNA1S p.Arg1239Gly VAR_001501 rs28930069
3 CACNA1S p.Arg1239His VAR_001502 rs28930068
4 CACNA1S p.Arg528Gly VAR_054953 rs80338778
5 CACNA1S p.Arg900Ser VAR_054954

ClinVar genetic disease variations for Hypokalemic Periodic Paralysis, Type 1:

6 (show all 14)
id Gene Variation Type Significance SNP ID Assembly Location
1 SCN4A NM_000334.4(SCN4A): c.2006G> A (p.Arg669His) single nucleotide variant Pathogenic rs80338784 GRCh37 Chromosome 17, 62036638: 62036638
2 SCN4A NM_000334.4(SCN4A): c.2015G> A (p.Arg672His) single nucleotide variant Pathogenic rs80338788 GRCh37 Chromosome 17, 62036629: 62036629
3 SCN4A NM_000334.4(SCN4A): c.2014C> G (p.Arg672Gly) single nucleotide variant Pathogenic rs80338785 GRCh37 Chromosome 17, 62036630: 62036630
4 SCN4A NM_000334.4(SCN4A): c.2014C> A (p.Arg672Ser) single nucleotide variant Pathogenic rs80338785 GRCh37 Chromosome 17, 62036630: 62036630
5 CACNA1S NM_000069.2(CACNA1S): c.3716G> A (p.Arg1239His) single nucleotide variant Pathogenic rs28930068 GRCh37 Chromosome 1, 201022666: 201022666
6 CACNA1S NM_000069.2(CACNA1S): c.3715C> G (p.Arg1239Gly) single nucleotide variant Pathogenic rs28930069 GRCh37 Chromosome 1, 201022667: 201022667
7 CACNA1S NM_000069.2(CACNA1S): c.1583G> A (p.Arg528His) single nucleotide variant Pathogenic rs80338777 GRCh37 Chromosome 1, 201047043: 201047043
8 CACNA1S NM_000069.2(CACNA1S): c.2627T> A (p.Val876Glu) single nucleotide variant Pathogenic rs267606698 GRCh37 Chromosome 1, 201036045: 201036045
9 CACNA1S NM_000069.2(CACNA1S): c.1582C> G (p.Arg528Gly) single nucleotide variant Pathogenic rs80338778 GRCh37 Chromosome 1, 201047044: 201047044
10 SCN4A NM_000334.4(SCN4A): c.2014C> T (p.Arg672Cys) single nucleotide variant Pathogenic rs80338785 GRCh37 Chromosome 17, 62036630: 62036630
11 SCN4A NM_000334.4(SCN4A): c.3395G> A (p.Arg1132Gln) single nucleotide variant Pathogenic rs80338789 GRCh37 Chromosome 17, 62024451: 62024451
12 KCNJ2 NM_000891.2(KCNJ2): c.161G> T (p.Cys54Phe) single nucleotide variant Pathogenic rs199473650 GRCh37 Chromosome 17, 68171341: 68171341
13 CACNA1S NM_000069.2(CACNA1S): c.2748C> G (p.His916Gln) single nucleotide variant Pathogenic rs2297902 GRCh38 Chromosome 1, 201065943: 201065943
14 CACNA1S NM_000069.2(CACNA1S): c.3526-2A> G single nucleotide variant Pathogenic rs797045031 GRCh38 Chromosome 1, 201058493: 201058493

Expression for Hypokalemic Periodic Paralysis, Type 1

Search GEO for disease gene expression data for Hypokalemic Periodic Paralysis, Type 1.

Pathways for Hypokalemic Periodic Paralysis, Type 1

Pathways related to Hypokalemic Periodic Paralysis, Type 1 according to GeneCards Suite gene sharing:

(show all 19)
id Super pathways Score Top Affiliating Genes
1
Show member pathways
12.61 CACNA1C CACNA1S CACNB4 INS KCNJ2 RYR1
2
Show member pathways
12.54 CACNA1C CACNA1S KCNJ2 RYR1
3
Show member pathways
12.34 ATP6V0A4 CLCN1 RYR1 TRDN
4
Show member pathways
12.34 CACNA1C CACNA1S CACNB4 KCNE3 KCNE4 KCNJ2
5
Show member pathways
12.3 CACNA1C CACNA1S CACNB4 RYR1
6
Show member pathways
12.03 CACNA1C CACNA1S RYR1
7 11.99 CACNA1C CACNA1S CACNB4 KCNE3 KCNE4 KCNJ2
8
Show member pathways
11.98 CACNA1C CACNA1S CACNB4
9 11.89 CACNA1C CACNA1S CACNB4 RYR1
10
Show member pathways
11.85 CACNA1C CACNA1S CACNB4
11
Show member pathways
11.8 CACNA1C CACNA1S CLCN1 INS
12 11.58 CACNA1C CACNA1S CACNB4
13 11.48 CACNA1C CACNA1S KCNJ2
14 11.42 CACNA1C CACNA1S CACNB4
15 11.37 CACNA1C KCNE3 KCNE4 KCNJ2
16 11.25 CACNA1C CACNA1S CACNB4 RYR1
17 11.2 CACNA1C CACNA1S CACNB4
18
Show member pathways
10.98 CACNA1C CACNA1S CACNB4 KCNE3 KCNE4 SCN4A
19 10.6 CACNA1S RYR1

GO Terms for Hypokalemic Periodic Paralysis, Type 1

Cellular components related to Hypokalemic Periodic Paralysis, Type 1 according to GeneCards Suite gene sharing:

id Name GO ID Score Top Affiliating Genes
1 smooth endoplasmic reticulum GO:0005790 9.46 KCNJ2 RYR1
2 I band GO:0031674 9.43 CACNA1S RYR1
3 junctional sarcoplasmic reticulum membrane GO:0014701 9.32 RYR1 TRDN
4 L-type voltage-gated calcium channel complex GO:1990454 9.26 CACNA1C CACNA1S
5 junctional membrane complex GO:0030314 9.16 RYR1 TRDN
6 T-tubule GO:0030315 9.13 CACNA1S KCNJ2 RYR1
7 voltage-gated calcium channel complex GO:0005891 8.92 CACNA1C CACNA1S CACNB4 TRDN
8 integral component of membrane GO:0016021 10.14 ATP6V0A4 CACNA1C CACNA1S CLCN1 KCNE3 KCNE4
9 plasma membrane GO:0005886 10.11 ATP6V0A4 CACNA1C CACNA1S CACNB4 CLCN1 KCNE3

Biological processes related to Hypokalemic Periodic Paralysis, Type 1 according to GeneCards Suite gene sharing:

(show all 19)
id Name GO ID Score Top Affiliating Genes
1 transmembrane transport GO:0055085 9.91 CACNA1C CACNA1S CLCN1 RYR1 SCN4A
2 transport GO:0006810 9.9 ATP6V0A4 CACNA1C CACNA1S CACNB4 CLCN1 KCNE3
3 ion transmembrane transport GO:0034220 9.77 ATP6V0A4 CLCN1 RYR1 SCN4A TRDN
4 calcium ion transport GO:0006816 9.76 CACNA1C CACNA1S CACNB4 RYR1
5 potassium ion transport GO:0006813 9.74 KCNE3 KCNE4 KCNJ2
6 potassium ion transmembrane transport GO:0071805 9.73 KCNE3 KCNE4 KCNJ2
7 cellular calcium ion homeostasis GO:0006874 9.71 RYR1 TRDN XK
8 calcium ion transmembrane transport GO:0070588 9.71 CACNA1C CACNA1S CACNB4 RYR1
9 muscle contraction GO:0006936 9.65 CACNA1S CLCN1 RYR1 SCN4A TRDN
10 ion transport GO:0006811 9.65 ATP6V0A4 CACNA1C CACNA1S CACNB4 CLCN1 KCNE3
11 cardiac conduction GO:0061337 9.62 CACNA1C CACNA1S CACNB4 KCNJ2
12 regulation of heart rate by cardiac conduction GO:0086091 9.61 CACNA1C KCNE3 KCNJ2
13 skeletal muscle fiber development GO:0048741 9.58 RYR1 XK
14 membrane depolarization during action potential GO:0086010 9.58 CACNA1S SCN4A
15 cardiac muscle cell action potential involved in contraction GO:0086002 9.55 CACNA1C KCNJ2
16 membrane depolarization during cardiac muscle cell action potential GO:0086012 9.52 CACNA1C KCNJ2
17 cellular response to caffeine GO:0071313 9.49 CACNA1S RYR1
18 release of sequestered calcium ion into cytosol by sarcoplasmic reticulum GO:0014808 9.48 RYR1 TRDN
19 regulation of ion transmembrane transport GO:0034765 9.28 CACNA1C CACNA1S CACNB4 CLCN1 KCNE3 KCNE4

Molecular functions related to Hypokalemic Periodic Paralysis, Type 1 according to GeneCards Suite gene sharing:

id Name GO ID Score Top Affiliating Genes
1 calcium channel activity GO:0005262 9.56 CACNA1C CACNA1S CACNB4 RYR1
2 ion channel binding GO:0044325 9.54 KCNE3 KCNE4 TRDN
3 ion channel activity GO:0005216 9.5 CACNA1C RYR1 SCN4A
4 voltage-gated ion channel activity GO:0005244 9.35 CACNA1C CACNA1S CLCN1 KCNJ2 SCN4A
5 high voltage-gated calcium channel activity GO:0008331 9.33 CACNA1C CACNA1S CACNB4
6 voltage-gated calcium channel activity GO:0005245 8.92 CACNA1C CACNA1S CACNB4 RYR1

Sources for Hypokalemic Periodic Paralysis, Type 1

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 Orphanet
67 TGDB
68 Tocris
69 UMLS
70 UMLS via Orphanet
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