National Hospital Organization

Voltage-gated sodium channel Nav1.7, encoded by the SCN9A gene, has been linked to diverse painful peripheral neuropathies, represented by the inherited erythromelalgia (EM) and paroxysmal extreme pain disorder (PEPD). The aim of this study was to determine the genetic etiology of patients experiencing neuropathic pain, and shed light on the underlying pathogenesis. We enrolled eight patients presenting with early-onset painful peripheral neuropathies, consisting of six cases exhibiting EM/EM-like disorders and two cases clinically diagnosed with PEPD. We conducted a gene-panel sequencing targeting 18 genes associated with hereditary sensory and/or autonomic neuropathy. We introduced novel SCN9A mutation (F1624S) into a GFP-2A-Nav1.7rNS plasmid, and the constructs were then transiently transfected into HEK293 cells. We characterized both wild-type and F1624S Nav1.7 channels using an automated high-throughput patch-clamp system. From two patients displaying EM-like/EM phenotypes, we identified two SCN9A mutations, I136V and P1308L. Among two patients diagnosed with PEPD, we found two additional mutations in SCN9A, F1624S (novel) and A1632E. Patch-clamp analysis of Nav1.7-F1624S revealed depolarizing shifts in both steady-state fast inactivation (17.4 mV, p < .001) and slow inactivation (5.5 mV, p < .001), but no effect on channel activation was observed. Clinical features observed in our patients broaden the phenotypic spectrum of SCN9A-related pain disorders, and the electrophysiological analysis enriches the understanding of genotype-phenotype association caused by Nav1.7 gain-of-function mutations.

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Erythromelalgia Caused by Polycythemia Vera Combined with Primary Aldosteronism.

Suzuki M, Watari T

European journal of case reports in internal medicine • 2020-01-01

A 61-year-old woman with a history of primary aldosteronism caused by unilateral hyperplasia of the adrenal gland presented with a 2-week history of redness and severe pain in the right thumb and thenar regions. She had initially visited a dermatologist and was diagnosed with cellulitis and treated with cefditoren pivoxil for 5 days, but there was no improvement. The pain worsened and was accompanied by a burning sensation. The dermatologist prescribed famciclovir for 5 days owing to suspicion of herpes zoster. The patient was then referred to our department because her symptoms persisted. Physical examination showed no abnormalities other than the redness in the right thumb and thenar regions and spontaneous moderate pain present throughout the right thumb. Investigations revealed normal blood chemistry and coagulation factor levels, except for elevated haemoglobin (18.2 g/dl). Further investigations revealed an erythropoietin level of 2.3 IU/ml and Janus kinase 2 mutation. Hence, we diagnosed the patient with erythromelalgia caused by polycythemia vera. In this report, we discuss the treatment of polycythemia causing erythromelalgia, and the aetiology of primary aldosteronism and polycythemia vera. Polycythemia can cause erythromelalgia, which should be treated with aspirin.Primary aldosteronism causes secondary erythropoiesis through activation of the renin-aldosterone system, but the mechanism is not clear.Erythropoiesis may be promoted by concurrent primary aldosteronism and polycythemia vera, resulting in secondary erythromelalgia.

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