Erythromelalgia malady

Genetics Home Reference: Erythromelalgia is a condition characterized by episodes of pain, redness, and swelling in various parts of the body, particularly the hands and feet. These episodes are usually triggered by increased body temperature, which may be caused by exercise or entering a warm room. Ingesting alcohol or spicy foods may also trigger an episode. Wearing warm socks, tight shoes, or gloves can cause a pain episode so debilitating that it can impede everyday activities such as wearing shoes and walking. Pain episodes can prevent an affected person from going to school or work regularly.¹⁷

MalaCards: Erythromelalgia, also known as primary erythermalgia, is related to erythermalgia and essential thrombocythemia. An important gene associated with Erythromelalgia is SCN9A (sodium channel, voltage-gated, type IX, alpha subunit), and among its related pathways are Sodium channels and transporters- inward current and GHRH Signaling. The compounds ppbp and cellulose triacetate have been mentioned in the context of this disorder. Affiliated tissues include skin, t cells and endothelial.

NIH Rare Diseases: Erythromelalgia (EM), is a rare disorder that is characterized by episodes of burning pain, warmth, and redness in the hands and feet. The cause of the symptoms in erythromelalgia is unknown.³⁰

Wikipedia: Erythromelalgia, also known as Mitchell\'s disease (after Silas Weir Mitchell), acromelalgia, red...⁴⁴ more...

OMIM: 133020

Aliases & Descriptions:

erythromelalgia 6 30 17 8 32 43 primary erythermalgia 30 43 erythromelalgia (disorder) 6 familial erythromelalgia 17

primary erythromelalgia 17 erythermalgia, primary 33 erythermalgia 17

Diseases related to erythromelalgia by text searches and GeneDecks gene sharing:

(show all 39)

id	Related Disease	Score	Top Affiliating Genes
1	erythermalgia	32.5	SCN7A, SCN9A
2	essential thrombocythemia	27.8	PPBP, PF4, THBD
3	mitral valve stenosis	13.3	PF4, PPBP
4	peripheral vascular disease	13.2	PPBP, PF4
5	thrombotic thrombocytopenic purpura, acquired	13.1	PPBP, THBD
6	venous tributary occlusion of retina	13.1	PPBP, THBD, PF4
7	adult respiratory distress syndrome	13.1	THBD, PPBP
8	heparin-induced thrombocytopenia	13.1	THBD, PF4, PPBP
9	hemorrhagic disease	13.1	PF4, THBD, PPBP
10	intermittent claudication	13.0	PPBP, PF4, THBD
11	thrombophilia	13.0	PF4, PPBP, THBD
12	disseminated intravascular coagulation	13.0	THBD, PPBP, PF4
13	polycythemia vera	12.9	THBD, PPBP, PF4
14	systemic scleroderma	12.9	THBD, PF4, PPBP
15	febrile seizures	12.8	SCN9A, SCN7A, SCN8A
16	legg-calve-perthes disease	12.8	THBD, PEPD
17	uremia	12.8	THBD, PPBP, PF4
18	generalized epilepsy with febrile seizures plus	12.8	SCN8A, SCN9A, SCN7A
19	thrombocytosis	12.7	PPBP, PF4, EIF4ENIF1, THBD
20	purpura	12.7	SCN4B, PPBP, PF4, THBD
21	migraine without aura	12.7	SCN9A, THBD, PPBP, PF4
22	polycythemia	12.7	THBD, PPBP, PF4, EIF4ENIF1
23	myotonia	12.7	SCN8A, PSMC4, SCN7A
24	hypercholesterolemia	12.6	PF4, PPBP, LIN9, THBD
25	myeloproliferative disorder	12.6	PPBP, PF4, THBD
26	trigeminal neuralgia	12.5	SCN9A, SCN3A
27	essential hypertension	12.4	PF4, THBD, CPSF4, PPBP, SCN7A
28	cerebral infarction	12.4	PPBP, PF4, THBD
29	vasculitis	12.4	PF4, PPBP, THBD, PEPD
30	coronary heart disease	12.3	THBD, PF4, PPBP, LIN9
31	atrial fibrillation	12.2	PF4, THBD, PPBP, SCN4B, PEPD
32	long qt syndrome	12.1	SCN8A, SCN3A, SCN4B
33	hypertension	11.4	PPBP, SCN7A, THBD, PEPD, PF4, CPSF4
34	brugada syndrome	11.3	PSMC4, SCN8A, SCN4B, NAV1, SCN3A
35	neuronitis	7.4
36	paroxysmal extreme pain disorder	7.0
37	scn9a-related inherited erythromelalgia	7.0
38	pain disorder	5.6
39	paine syndrome	5.6

Clinical features from OMIM: 133020

Approved drugs:

Drug clinical trials:

MalaCards organs/tissues related to erythromelalgia:

²²

Articles related to erythromelalgia:

(show all 19)

id	Title	Authors	Year	Affiliating Genes
1	Nav1.7 mutations associated with paroxysmal extreme p ain disorder, but not erythromelalgia, enhance Navbeta4 peptide-mediated resurg ent sodium currents. (21115638)	Theile J.W.... Cummins T.R.	2011	SCN9A, SCN4B
2	Deletion mutation of sodium channel Na(V)1.7 in inher ited erythromelalgia: enhanced slow inactivation modulates dorsal root ganglion neuron hyperexcitability. (21705421)	Cheng X.... Waxman S.G.	2011	SCN9A
3	Alternative splicing may contribute to time-dependent manifestation of inherited erythromelalgia. (20478850)	Choi J.S.... Waxman S.G.	2010	SCN9A
4	Treatment with carbamazepine and gabapentin of a pati ent with primary erythermalgia (erythromelalgia) identified to have a mutation in the SCN9A gene, encoding a voltage-gated sodium channel. (19549232)	Natkunarajah J.... Mortimer P.	2009	SCN9A
5	Early- and late-onset inherited erythromelalgia: genotype-phenotype correlation. (19369487)	Han C.... Waxman S.G.	2009	SCN9A
6	A novel Nav1.7 mutation producing carbamazepine-respo nsive erythromelalgia. (19557861)	Fischer T.Z.... Waxman S.G.	2009	SCN9A
7	Erythromelalgia mutation L823R shifts activation and inactivation of threshold sodium channel Nav1.7 to hyperpolarized potentials. (19800314)	Lampert A.... Waxman S.G.	2009	SCN9A
8	A pore-blocking hydrophobic motif at the cytoplasmic aperture of the closed-state Nav1.7 channel is disrupted by the erythromelalgia-associated F1449V mutation. (18550534)	Lampert A.... Waxman S.G.	2008	PSMC4
9	Mutation I136V alters electrophysiological properties of the Na(v)1.7 channel in a family with onset of erythromelalgia in the second decade. (18171466)	Cheng X.... Waxman S.G.	2008	SCN9A
10	NaV1.7 gain-of-function mutations as a continuum: A1632E displays physiological changes associated with erythromelalgia and paroxysmal extreme pain disorder mutations and produces symptoms of both disorders. (18945915)	Estacion M.... Waxman S.G.	2008	SCN9A
11	A case of inherited erythromelalgia. (17410110)	Novella S.P.... Waxman S.G.	2007	SCN9A
12	A Nav1.7 channel mutation associated with hereditary erythromelalgia contributes to neuronal hyperexcitability and displays reduced lidocaine sensitivity. (17430993)	Sheets P.L.... Cummins T.R.	2007	SCN9A
13	Characterization of a familial case with primary erythromelalgia from Taiwan. (17294067)	Lee M.J.... Yang C.C.	2007	SCN9A
14	Temperature dependence of erythromelalgia mutation L858F in sodium channel Nav1.7. (17239250)	Han C.... Waxman S.G.	2007	SCN9A
15	Na(V)1.7 mutant A863P in erythromelalgia: effects of altered activation and steady-state inactivation on excitability of nociceptive dorsal root ganglion neurons. (17135418)	Harty T.P.... Waxman S.G.	2006	SCN9A
16	Size matters: Erythromelalgia mutation S241T in Nav1.7 alters channel gating. (17008310)	Lampert A.... Waxman S.G.	2006	SCN9A
17	Gain-of-function mutation in Nav1.7 in familial erythromelalgia induces bursting of sensory neurons. (15958509)	Dib-Hajj S.D.... Waxman S.G.	2005	SCN9A
18	Erythromelalgia: a hereditary pain syndrome enters the molecular era. (15929046)	Waxman S.G.... Dib-Hajj S.D.	2005	SCN9A
19	Erythromelalgia in essential thrombocythemia is characterized by platelet activation and endothelial cell damage but not by thrombin generation. (8883266)	van Genderen P.J.... Michiels J.J.	1996	THBD, PPBP, PF4

Genes related to erythromelalgia according to GeneCards:

(show all 15)

id	Symbol	Description	Score	GeneCards Section Context
1	SCN9A	sodium channel, voltage-gated, type IX, alpha subunit	11.0	Publications
2	SCN7A	sodium channel, voltage-gated, type VII, alpha subunit	11.0
3	PPBP	pro-platelet basic protein (chemokine (C-X-C motif) ligand 7)	11.0	Publications
4	PF4	platelet factor 4	11.0	Publications
5	THBD	thrombomodulin	11.0	Publications
6	SCN4B	sodium channel, voltage-gated, type IV, beta subunit	11.0	Publications
7	ADHFE1	alcohol dehydrogenase, iron containing, 1	11.0	Disorders
8	EIF4ENIF1	eukaryotic translation initiation factor 4E nuclear import factor 1	11.0
9	LIN9	lin-9 homolog (C. elegans)	11.0
10	CPSF4	cleavage and polyadenylation specific factor 4, 30kDa	11.0
11	PSMC4	proteasome (prosome, macropain) 26S subunit, ATPase, 4	11.0	Publications
12	SCN3A	sodium channel, voltage-gated, type III, alpha subunit	11.0
13	SCN8A	sodium channel, voltage gated, type VIII, alpha subunit	11.0
14	NAV1	neuron navigator 1	11.0	Disorders
15	PEPD	peptidase D	11.0

Pathways related to erythromelalgia according to GeneDecks:

id	Pathway	Score	Top Affiliating Genes
1	Sodium channels and transporters- inward current10	9.1	SCN3A, SCN9A, SCN8A
2	GHRH Signaling36	8.7	SCN7A, SCN4B, SCN3A, SCN9A, SCN8A
3	Aldosterone Signaling in Epithelial Cells36	8.7	SCN8A, SCN9A, SCN3A, SCN4B, SCN7A
4	Cholera Infection36	8.7	SCN8A, SCN9A, SCN3A, SCN4B, SCN7A
5	Neuropathic Pain-Signaling in Dorsal Horn Neurons36	8.6	SCN8A, SCN9A, SCN3A, SCN4B, SCN7A
6	Activation of cAMP-Dependent PKA36	8.3	PPBP, SCN8A, SCN9A, SCN3A, SCN4B, SCN7A
7	PKA Signaling36	8.3	SCN8A, SCN9A, SCN3A, SCN4B, SCN7A
8	cAMP Pathway36	8.2	PPBP, SCN8A, SCN9A, SCN3A, SCN4B, SCN7A

Compounds related to erythromelalgia according to GeneDecks:

(show all 30)

id	Compound	Score	Top Affiliating Genes
1	ppbp32	10.3	PPBP, PF4
2	cellulose triacetate32	10.3	PPBP, PF4
3	fibrinopeptide a32	10.2	THBD, PF4
4	fondaparinux32	10.2	PF4, THBD
5	iohexol32	10.2	PPBP, PF4
6	sertraline32 34 9 18 9	14.1	PPBP, PF4
7	Drotrecogin alfa9 9	11.1	THBD, PF4
8	11-dehydrothromboxane b232	10.0	THBD, PF4, PPBP
9	6-ketoprostaglandin f1alpha32	10.0	THBD, PF4, PPBP
10	ptca32	10.0	PPBP, PF4, THBD
11	iloprost32 42 9 9	13.0	THBD, PF4, PPBP
12	txb232	10.0	THBD, PF4, PPBP
13	warfarin32 34 9 18 9	14.0	THBD, PF4, PPBP
14	thromboxane32 18	11.0	PPBP, PF4, THBD
15	pge132	9.9	PPBP, PF4, THBD
16	aprotinin32 9 9	11.9	THBD, PF4, PPBP
17	gamma-carboxyglutamic acid32	9.8	THBD, PF4
18	citrate32	9.8	PPBP, PF4, THBD
19	zonisamide32 9 9	11.8	SCN4B, SCN3A, SCN9A
20	heparan sulfate32 18	10.7	PPBP, PF4, THBD
21	ticlopidine32 9 9	11.7	PF4, PPBP
22	aspirin32 34 18	11.5	PEPD, THBD, PF4, PPBP
23	flecainide acetate42	9.4	SCN8A, SCN3A, SCN4B
24	hyaluronic acid32 18	10.4	PPBP, THBD, PEPD
25	ralfinamide mesylate42	9.4	SCN8A, SCN3A, SCN4B
26	qx 314 chloride42	9.4	SCN8A, SCN3A, SCN4B
27	tetrodotoxin citrate42	9.4	SCN8A, SCN3A, SCN4B
28	vinpocetine32 42	10.4	SCN4B, SCN3A, SCN8A
29	alanine32	8.8	PEPD, PSMC4, THBD, PF4, PPBP
30	sodium32 18	8.9	SCN7A, PSMC4, THBD, PF4, SCN8A, SCN9A

Cellular components related to erythromelalgia according to GeneDecks:

id	Name	GO ID	Score	Top Affiliating Genes
1	voltage-gated sodium channel complex	GO:001518	8.6	SCN7A, SCN4B, SCN3A, SCN9A, SCN8A

Biological processes related to erythromelalgia according to GeneDecks:

id	Name	GO ID	Score	Top Affiliating Genes
1	sodium ion transport	GO:006814	8.6	SCN7A, SCN4B, SCN3A, SCN9A, SCN8A

Molecular functions related to erythromelalgia according to GeneDecks:

id	Name	GO ID	Score	Top Affiliating Genes
1	voltage-gated sodium channel activity	GO:005248	8.6	SCN7A, SCN4B, SCN3A, SCN9A, SCN8A