Manifestation, Management and Molecular Analysis of Candidate Genes in Two Rare Cases of Thyrotoxic Hypokalemic Periodic Paralysis

Abstract

Background: Hypokalemic periodic paralysis as a complication of thyrotoxicosis (THypoKPP) is common in Asians but not well recognized in Western countries or pediatric patients, where most cases are due to the familial variant (FHypoKPP). Ion channel gene mutations may underlie these diseases. We describe the first pediatric and a rare adult Caucasian case of THypoKPP in Finland. Methods: Manifestation and management of two THypoKPP cases. We studied for possible mutations in KCNE3, KCNJ2, SCN4A and CACNA1S genes. Results: A 15-year-old Vietnamese boy presented with sudden-onset paralysis and severe hypokalemia, 1.8 mmol/l. The case was first regarded as FHypoKPP, but thyroid function testing revealed a suppressed TSH and highly elevated FT4. A 37-year-old Caucasian male presented with acute tetraparesis. His plasma potassium was only 1.4 mmol/l. Treatment with carbimazole had been initiated two weeks earlier, but FT4 was still elevated. No mutations in KCNE3, KCNJ2, SCN4A or CACNA1S genes were detected. Conclusions: THypoKPP is a potentially life-threatening condition which bares many similarities with FHypoKPP. THypoKPP is rare in Western countries but should be considered in sudden-onset paralysis, independently of age and especially in males. Mutations in ion channel candidate genes did not underlie the disease in the present cases.

Concurrence of Thyrotoxicosis and Gitelman’s Syndrome-Associated Hypokalemia-Induced Periodic Paralysis

“…Hypokalemia-induced periodic paralysis in adolescents comprises sporadic or familial thyrotoxic hypokalemic periodic paralysis (THPP) secondary to thyrotoxicosis, 1–4 and the hereditary syndrome of Gitelman. 5–9 THPP is a common complication of hyperthyroidism in Asian men and manifests as recurrent episodic muscle weakness with hypokalemia and thyrotoxicosis.…”

“…1,3 In familial cases, it is due to an association of mutation in the KCNE3 (voltage-gated potassium channel) gene. 2,4 In contrast, Gitelman's syndrome has been attributed to mutations in the solute carrier family 12 member 3 gene ( SLC12A3 ) encoding thiazide-sensitive Na + /Cl − cotransporter of the distal tubule, respectively. 5–9 Gitelman's syndrome is an autosomal recessive disorder that commonly presents in older children or young adults and manifests clinically as hypokalemic hypomagnesemic hypocalciuria with metabolic alkalosis.…”

Thyrotoxic periodic paralysis in an Italian man: clinical manifestation and genetic analysis

“…In Europeans, the SNP 1551 T . C has been reported only in one patient, 23 with our patient being the second one. The exact role of these SNPs in the pathogenesis of TPP is unclear.…”

Unusual case of weakness in the UK

“…Although rare, there have been increasing cases of HTPP reported in European populations1–5 as well as some cases reported in children 7…”