TTPP1
MCID: THY084
MIFTS: 35

Thyrotoxic Periodic Paralysis 1 (TTPP1)

Categories: Endocrine diseases, Genetic diseases, Neuronal diseases, Rare diseases

Aliases & Classifications for Thyrotoxic Periodic Paralysis 1

MalaCards integrated aliases for Thyrotoxic Periodic Paralysis 1:

Name: Thyrotoxic Periodic Paralysis 1 56 73
Thyrotoxic Periodic Paralysis, Susceptibility to, 1 56 29 13 6
Thyrotoxic Hypokalemic Periodic Paralysis 73 36
Ttpp1 56 73
Tpp 73

Characteristics:

OMIM:

56
Inheritance:
autosomal dominant

Miscellaneous:
genetic heterogeneity
more frequent in males
attacks precipitated by hypokalemia, administration of glucose or insulin, heavy carbohydrate consumption, stress, fatigue, rest after exercise
attacks may present during or after sleep
usually occurs in young adulthood
muscle weakness occurs only in the presence of hyperthyroidism
more frequent in individuals of asian descent
complete recovery upon treatment of hyperthyroidism


HPO:

31
thyrotoxic periodic paralysis 1:
Inheritance autosomal dominant inheritance heterogeneous sporadic


Classifications:



Summaries for Thyrotoxic Periodic Paralysis 1

OMIM : 56 Thyrotoxic periodic paralysis is a sporadic muscle disorder characterized by episodic attacks of weakness associated with hypokalemia in individuals with hyperthyroidism. The paralysis resolves upon treatment of hyperthyroidism. The disorder is most common among males of Asian descent, including Chinese, Japanese, Vietnamese, Filipino, and Koreans, although it occurs less commonly in individuals of Caucasian background. Thyrotoxic periodic paralysis is clinically similar to hereditary hypokalemic periodic paralysis (HOKPP; 170400), but the paralysis in TTPP occurs only in the presence of hyperthyroidism. TTPP can also be precipitated by factors that result in hypokalemia, such as carbohydrate ingestion and rest after exercise (review by Kung, 2006). (188580)

MalaCards based summary : Thyrotoxic Periodic Paralysis 1, also known as thyrotoxic periodic paralysis, susceptibility to, 1, is related to thyrotoxic periodic paralysis and hypokalemic periodic paralysis, type 1. An important gene associated with Thyrotoxic Periodic Paralysis 1 is CACNA1S (Calcium Voltage-Gated Channel Subunit Alpha1 S), and among its related pathways/superpathways are Circadian entrainment and Oxytocin signaling pathway. Affiliated tissues include thyroid, and related phenotypes are muscle weakness and hypokalemia

KEGG : 36 Thyrotoxic hypokalemic periodic paralysis (TPP) is characterized by thyrotoxicosis in combination with typical episodes of hypokalemic periodic paralysis (HypoPP). People of Asian descent are most often affected, but all ethnicities can present with TPP. Hypokalemia is typical during paralysis, but is not always detected; administration of potassium during the attacks should be offered cautiously, preferably orally, to prevent rebound hyperkalemia. Mutations have been identified in TPP patients in an inwardly rectifying potassium channel, , that is expressed in muscle and transcriptionally regulated by thyroid hormone. Mutations in Kir2.6, which occur in up to 33% of patients, reinforces the hypothesis of genetic heterogeneity in patients with TPP.

UniProtKB/Swiss-Prot : 73 Thyrotoxic periodic paralysis 1: A sporadic muscular disorder characterized by episodic weakness and hypokalemia during a thyrotoxic state. It is clinically similar to hereditary hypokalemic periodic paralysis, except for the fact that hyperthyroidism is an absolute requirement for disease manifestation. The disease presents with recurrent episodes of acute muscular weakness of the four extremities that vary in severity from paresis to complete paralysis. Attacks are triggered by ingestion of a high carbohydrate load or strenuous physical activity followed by a period of rest. Thyrotoxic periodic paralysis can occur in association with any cause of hyperthyroidism, but is most commonly associated with Graves disease.

Related Diseases for Thyrotoxic Periodic Paralysis 1

Diseases in the Thyrotoxic Periodic Paralysis family:

Thyrotoxic Periodic Paralysis 1 Thyrotoxic Periodic Paralysis 2
Thyrotoxic Periodic Paralysis 3

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

(show top 50) (show all 83)
# Related Disease Score Top Affiliating Genes
1 thyrotoxic periodic paralysis 32.7 KCNJ18 CACNA1S
2 hypokalemic periodic paralysis, type 1 31.1 KCNJ18 CACNA1S
3 periodic paralysis 31.1 KCNJ18 CACNA1S
4 graves disease 1 30.7 KCNJ18 CACNA1S
5 hypokalemia 30.5 KCNJ18 CACNA1S
6 hyperthyroidism 30.2 KCNJ18 CACNA1S
7 familial periodic paralysis 29.8 KCNJ18 CACNA1S
8 andersen cardiodysrhythmic periodic paralysis 29.7 KCNJ18 CACNA1S
9 thyrotoxic periodic paralysis 2 12.1
10 thiamine metabolism dysfunction syndrome 5 11.4
11 graves' disease 10.8
12 goiter 10.5
13 quadriplegia 10.4
14 tremor 10.4
15 glioma 10.3
16 glial tumor 10.3
17 myasthenia gravis 10.2
18 stroke, ischemic 10.2
19 branchiootic syndrome 1 10.2
20 alpha/beta t-cell lymphopenia with gamma/delta t-cell expansion, severe cytomegalovirus infection, and autoimmunity 10.2
21 encephalopathy, progressive, early-onset, with episodic rhabdomyolysis 10.2
22 hypophosphatemia 10.2
23 hypothyroidism 10.2
24 hyperinsulinism 10.2
25 transient cerebral ischemia 10.2
26 papillary carcinoma 10.2
27 myopathy 10.2
28 thyroiditis 10.2
29 pathologic nystagmus 10.2
30 familial periodic paralyses 10.2
31 periodic paralyses 10.2
32 beriberi 10.2
33 neuronal ceroid lipofuscinosis 10.2
34 hepatocellular carcinoma 10.1
35 helix syndrome 10.1
36 early-onset parkinson's disease 10.1
37 colon adenocarcinoma 10.1
38 autoimmune disease 10.0
39 colorectal cancer 10.0
40 hand skill, relative 10.0
41 huntington disease 10.0
42 parkinson disease, late-onset 10.0
43 phosphatase, acid, of tissues 10.0
44 prostate cancer 10.0
45 triiodothyronine receptor auxiliary protein 10.0
46 ceroid lipofuscinosis, neuronal, 2 10.0
47 ceroid storage disease 10.0
48 pyruvate carboxylase deficiency 10.0
49 prostatic hyperplasia, benign 10.0
50 neuronal ceroid-lipofuscinoses 10.0

Graphical network of the top 20 diseases related to Thyrotoxic Periodic Paralysis 1:



Diseases related to Thyrotoxic Periodic Paralysis 1

Symptoms & Phenotypes for Thyrotoxic Periodic Paralysis 1

Human phenotypes related to Thyrotoxic Periodic Paralysis 1:

31 (show all 9)
# Description HPO Frequency HPO Source Accession
1 muscle weakness 31 HP:0001324
2 hypokalemia 31 HP:0002900
3 weight loss 31 HP:0001824
4 hyperthyroidism 31 HP:0000836
5 goiter 31 HP:0000853
6 tachycardia 31 HP:0001649
7 periodic paralysis 31 HP:0003768
8 palpitations 31 HP:0001962
9 rhabdomyolysis 31 HP:0003201

Symptoms via clinical synopsis from OMIM:

56
Endocrine Features:
hyperthyroidism
goiter
enlarged thyroid gland

Growth Weight:
weight loss due to hyperthyroidism

Cardiovascular Vascular:
hypertension due to hyperthyroidism

Neurologic Central Nervous System:
tremor due to hyperthyroidism

Metabolic Features:
increased sweating due to hyperthyroidism

Cardiovascular Heart:
palpitations
tachycardia due to hyperthyroidism

Head And Neck Eyes:
exophthalmos due to hyperthyroidism

Muscle Soft Tissue:
muscle paralysis, episodic
muscle weakness, episodic
lower limbs more often affected
proximal muscles more often affected
recovery between attacks
more
Neurologic Peripheral Nervous System:
hypo- or areflexia during attacks

Laboratory Abnormalities:
hypokalemia during attacks
increased thyroid hormone
decreased tsh

Clinical features from OMIM:

188580

Drugs & Therapeutics for Thyrotoxic Periodic Paralysis 1

Search Clinical Trials , NIH Clinical Center for Thyrotoxic Periodic Paralysis 1

Genetic Tests for Thyrotoxic Periodic Paralysis 1

Genetic tests related to Thyrotoxic Periodic Paralysis 1:

# Genetic test Affiliating Genes
1 Thyrotoxic Periodic Paralysis, Susceptibility to, 1 29 CACNA1S

Anatomical Context for Thyrotoxic Periodic Paralysis 1

MalaCards organs/tissues related to Thyrotoxic Periodic Paralysis 1:

40
Thyroid

Publications for Thyrotoxic Periodic Paralysis 1

Articles related to Thyrotoxic Periodic Paralysis 1:

(show all 17)
# Title Authors PMID Year
1
Association of novel single nucleotide polymorphisms in the calcium channel alpha 1 subunit gene (Ca(v)1.1) and thyrotoxic periodic paralysis. 6 56
15001631 2004
2
Clinical review: Thyrotoxic periodic paralysis: a diagnostic challenge. 56
16608889 2006
3
No mutation in the KCNE3 potassium channel gene in Chinese thyrotoxic hypokalaemic periodic paralysis patients. 56
15212652 2004
4
Periodic paralysis mutation MiRP2-R83H in controls: Interpretations and general recommendation. 56
15037716 2004
5
Lack of association of the potassium channel-associated peptide MiRP2-R83H variant with periodic paralysis. 56
14504341 2003
6
A mutation in the KCNE3 potassium channel gene is associated with susceptibility to thyrotoxic hypokalemic periodic paralysis. 56
12414843 2002
7
Thyrotoxic hypokalemic periodic paralysis: report of four cases in black American males. 56
7711509 1994
8
Familial "hashitoxic' periodic paralysis. 56
3839536 1985
9
Familial periodic paralysis and hyperthyroidism. 56
290877 1979
10
Thyrotoxic periodic paralysis: a peculiar case with unusual dystonic behavior and variable relations of paralysis to serum potassium levels. 56
977720 1976
11
Hypokalaemic periodic paralysis complicating thyrotoxicosis. 56
1192145 1975
12
Thyrotoxic periodic paralysis. Effect of propranolol. 56
4432863 1974
13
Periodic paralysis caused by abuse of thyroid hormone. 56
4472229 1974
14
Thyrotoxic periodic paralysis. Periodic variation in the muscle calcium pump activity. 56
4260573 1972
15
Thyrotoxic periodic paralysis in Californians of Mexican and Filipino ancestry. 56
5059669 1972
16
Periodic paralysis complicating thyrotoxicosis in Chinese. 56
6017520 1967
17
Hypokalaemic periodic paralysis in rural northern India--most have secondary causes. 61
24275360 2014

Variations for Thyrotoxic Periodic Paralysis 1

ClinVar genetic disease variations for Thyrotoxic Periodic Paralysis 1:

6 (show all 16) ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎
# Gene Name Type Significance ClinVarId dbSNP ID GRCh37 Pos GRCh38 Pos
1 KCNJ18 NM_001194958.2(KCNJ18):c.429del (p.Ile144fs)deletion Pathogenic,risk factor 204 rs527236153 17:21703214-21703214
2 KCNJ18 NM_001194958.2(KCNJ18):c.1061C>T (p.Thr354Met)SNV Pathogenic,risk factor 205 rs527236158 17:356212-356212 17:21703847-21703847
3 KCNJ18 NM_001194958.2(KCNJ18):c.1097A>G (p.Lys366Arg)SNV Pathogenic,risk factor 207 rs527236159 17:356248-356248 17:21703883-21703883
4 KCNJ18 NM_001194958.2(KCNJ18):c.127C>T (p.Arg43Cys)SNV Pathogenic 143202 rs527236151 17:355278-355278 17:21702913-21702913
5 KCNJ18 NM_001194958.2(KCNJ18):c.419C>T (p.Thr140Met)SNV Pathogenic 143203 rs527236152 17:355570-355570 17:21703205-21703205
6 KCNJ18 NM_001194958.2(KCNJ18):c.502G>A (p.Val168Met)SNV Pathogenic 143205 rs527236154 17:355653-355653 17:21703288-21703288
7 KCNJ18 NM_001194958.2(KCNJ18):c.598G>C (p.Ala200Pro)SNV Pathogenic 143206 rs527236155 17:355749-355749 17:21703384-21703384
8 KCNJ18 NM_001194958.2(KCNJ18):c.1195C>T (p.Arg399Ter)SNV Pathogenic 143207 rs527236156 17:356346-356346 17:21703981-21703981
9 KCNJ18 NM_001194958.2(KCNJ18):c.1219C>T (p.Gln407Ter)SNV Pathogenic 143208 rs527236157 17:356370-356370 17:21704005-21704005
10 CACNA1S NM_000069.3(CACNA1S):c.3414+67A>GSNV risk factor 17629 rs28986463 1:201029719-201029719 1:201060591-201060591
11 CACNA1S NM_000069.3(CACNA1S):c.1385G>A (p.Arg462His)SNV Conflicting interpretations of pathogenicity 585658 rs146696298 1:201052298-201052298 1:201083170-201083170
12 CACNA1S NM_000069.3(CACNA1S):c.2767G>A (p.Val923Met)SNV Uncertain significance 473980 rs571902899 1:201035052-201035052 1:201065924-201065924
13 CACNA1S NM_000069.3(CACNA1S):c.93G>C (p.Leu31Phe)SNV Uncertain significance 474008 rs556751671 1:201081375-201081375 1:201112247-201112247
14 CACNA1S NM_000069.3(CACNA1S):c.253G>A (p.Gly85Ser)SNV Uncertain significance 567099 rs369931782 1:201079297-201079297 1:201110169-201110169
15 CACNA1S NM_000069.2(CACNA1S):c.-476G>ASNV Benign 17627 rs2281845 1:201081943-201081943 1:201112815-201112815
16 CACNA1S NM_000069.3(CACNA1S):c.258+57G>ASNV Benign 17628 rs1325310 1:201079235-201079235 1:201110107-201110107

Expression for Thyrotoxic Periodic Paralysis 1

Search GEO for disease gene expression data for Thyrotoxic Periodic Paralysis 1.

Pathways for Thyrotoxic Periodic Paralysis 1

Pathways related to Thyrotoxic Periodic Paralysis 1 according to GeneCards Suite gene sharing:

# Super pathways Score Top Affiliating Genes
1
Show member pathways
11.63 KCNJ18 CACNA1S
2
Show member pathways
11.08 KCNJ18 CACNA1S

GO Terms for Thyrotoxic Periodic Paralysis 1

Biological processes related to Thyrotoxic Periodic Paralysis 1 according to GeneCards Suite gene sharing:

# Name GO ID Score Top Affiliating Genes
1 ion transport GO:0006811 8.96 KCNJ18 CACNA1S
2 regulation of ion transmembrane transport GO:0034765 8.62 KCNJ18 CACNA1S

Molecular functions related to Thyrotoxic Periodic Paralysis 1 according to GeneCards Suite gene sharing:

# Name GO ID Score Top Affiliating Genes
1 voltage-gated ion channel activity GO:0005244 8.62 KCNJ18 CACNA1S

Sources for Thyrotoxic Periodic Paralysis 1

3 CDC
7 CNVD
9 Cosmic
10 dbSNP
11 DGIdb
17 EFO
18 ExPASy
19 FMA
28 GO
29 GTR
30 HMDB
31 HPO
32 ICD10
33 ICD10 via Orphanet
34 ICD9CM
35 IUPHAR
36 KEGG
37 LifeMap
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43 MeSH
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50 NDF-RT
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57 OMIM via Orphanet
61 PubMed
63 QIAGEN
68 SNOMED-CT via HPO
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72 UMLS via Orphanet
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