Details of Disease

General Information of Disease (ID: DISVIXI1)

• Disease Name: Hypokalemic periodic paralysis
• Synonyms: periodic paralysis I; HKPP; HOKPP; hypokalemic familial periodic paralysis; familial hypokalemic periodic paralysis; HypoPP; periodic hypokalemic paralysis; hypokalemic periodic paralysis; familial periodic paralysis (& [hypokalaemic]); Westphall disease
• Definition: Hypokalemic periodic paralysis (hypoPP) is characterized by episodes of muscle paralysis lasting from a few to 24-48 hours and associated with a fall in blood potassium levels.
• Disease Hierarchy:
  DISD9YAA: Familial periodic paralysis
  DIS6FOW8: Hypokalemia
  DISVIXI1: Hypokalemic periodic paralysis
• Disease Identifiers:
  MONDO ID: MONDO_0008223
  MESH ID: D020514
  UMLS CUI: C0238358
  MedGen ID: 116058
  Orphanet ID: 681
  SNOMED CT ID: 82732003

Molecular Interaction Atlas (MIA) of This Disease

This Disease Is Related to 11 DTT Molecule(s)

Gene Name	DTT ID	Evidence Level	Mode of Inheritance	REF
CACNA1S	TT94HRF	Limited	Genetic Variation	[1]
CACNA1S	TT94HRF	Supportive	Autosomal dominant	[2]
CLCN1	TTUYAF3	moderate	Genetic Variation	[3]
GABRA3	TT37EDJ	moderate	Genetic Variation	[4]
KCNQ5	TTWVL5Q	moderate	Biomarker	[5]
ATP1A2	TT5B6HJ	Strong	Biomarker	[6]
DPYD	TTZPS91	Strong	Genetic Variation	[7]
KCNJ18	TTVW8QH	Strong	Genetic Variation	[8]
KCNJ2	TTH7UO3	Strong	Genetic Variation	[9]
RYR1	TTU5CIX	Strong	Biomarker	[10]
SCN4A	TT84DRB	Definitive	Genetic Variation	[11]

This Disease Is Related to 1 DTP Molecule(s)

Gene Name	DTP ID	Evidence Level	Mode of Inheritance	REF
SCN4A	DT7SZIQ	Supportive	Autosomal dominant	[2]

This Disease Is Related to 6 DOT Molecule(s)

Gene Name	DOT ID	Evidence Level	Mode of Inheritance	REF
CACNA1S	OT96MCM2	Supportive	Autosomal dominant	[2]
SCN4A	OT0MYDHC	Supportive	Autosomal dominant	[2]
STAC3	OTPY3BGK	moderate	Altered Expression	[12]
DPYS	OTLTUIVL	Strong	Genetic Variation	[7]
FXYD1	OTNKT6GP	Strong	Biomarker	[13]
KCNE3	OTKWKR91	Strong	Genetic Variation	[14]

References

• [1] Prevalence and mutation spectrum of skeletal muscle channelopathies in the Netherlands.Neuromuscul Disord. 2018 May;28(5):402-407. doi: 10.1016/j.nmd.2018.03.006. Epub 2018 Mar 9.
• [2] Hypokalemic Periodic Paralysis. 2002 Apr 30 [updated 2018 Jul 26]. In: Adam MP, Feldman J, Mirzaa GM, Pagon RA, Wallace SE, Bean LJH, Gripp KW, Amemiya A, editors. GeneReviews(?) [Internet]. Seattle (WA): University of Washington, Seattle; 1993C2024.
• [3] Myotonia in a patient with a mutation in an S4 arginine residue associated with hypokalaemic periodic paralysis and a concomitant synonymous CLCN1 mutation.Sci Rep. 2019 Nov 26;9(1):17560. doi: 10.1038/s41598-019-54041-0.
• [4] Association of genetic variants in GABRA3 gene and thyrotoxic hypokalaemic periodic paralysis in Thai population.Clin Endocrinol (Oxf). 2008 Apr;68(4):646-51. doi: 10.1111/j.1365-2265.2007.03083.x. Epub 2007 Oct 29.
• [5] Expression patterns of two potassium channel genes in skeletal muscle cells of patients with familial hypokalemic periodic paralysis.Neurol India. 2011 Jul-Aug;59(4):527-31. doi: 10.4103/0028-3886.84331.
• [6] A novel ATP1A2 mutation in a patient with hypokalaemic periodic paralysis and CNS symptoms.Brain. 2018 Dec 1;141(12):3308-3318. doi: 10.1093/brain/awy283.
• [7] A novel sodium channel mutation in a family with hypokalemic periodic paralysis.Neurology. 1999 Dec 10;53(9):1932-6. doi: 10.1212/wnl.53.9.1932.
• [8] Rare KCNJ18 variants do not explain hypokalaemic periodic paralysis in 263 unrelated patients.J Neurol Neurosurg Psychiatry. 2016 Jan;87(1):49-52. doi: 10.1136/jnnp-2014-309293. Epub 2015 Apr 16.
• [9] Whole exome sequencing identified a heterozygous KCNJ2 missense variant underlying autosomal dominant familial hypokalemic periodic paralysis in a Pakistani family.J Pediatr Endocrinol Metab. 2019 Dec 18;32(12):1385-1389. doi: 10.1515/jpem-2019-0276.
• [10] Mutation analysis of two patients with hypokalemic periodic paralysis and suspected malignant hyperthermia.Muscle Nerve. 2004 Jul;30(1):114-7. doi: 10.1002/mus.20068.
• [11] Electromyographic Features in a Chinese Cohort With Hereditary Skeletal Muscle Channelopathies.J Clin Neurophysiol. 2020 May;37(3):231-238. doi: 10.1097/WNP.0000000000000635.
• [12] Stac3 enhances expression of human Ca(V)1.1 in Xenopus oocytes and reveals gating pore currents in HypoPP mutant channels.J Gen Physiol. 2018 Mar 5;150(3):475-489. doi: 10.1085/jgp.201711962. Epub 2018 Jan 31.
• [13] Phospholemman, a major regulator of skeletal muscle Na(+)/K(+)-ATPase, is not mutated in probands with hypokalemic periodic paralysis.Exp Ther Med. 2017 Oct;14(4):3229-3232. doi: 10.3892/etm.2017.4848. Epub 2017 Jul 28.
• [14] Strict bed rest following lumbar puncture in children and adolescents is of no benefit.Neurology. 2004 Mar 23;62(6):1003-5. doi: 10.1212/01.wnl.0000115387.67958.0f.