Thyrotoxic hypokalemic periodic paralysis (TPP) is a rare complication of hyperthyroidism characterized by episodes of muscle weakness and hypokalemia. The muscle weakness may be confined to a small group of muscles such as the forearm and hand muscles resulting in weakness of grip. Alternatively, the muscle weakness may be more generalized and the patient may be completely unable to move for hours, up to days at a time. Approximately 0.1% of Caucasians with hyperthyroidism develop TPP, while the incidence is up to 10 times higher in Latin American and Asian populations. Until recently, TPP was known to be associated with attacks of thyrotoxicosis and was previously thought not to be a genetic condition. In this study led by Dr Louis Ptacek at the University of California, researchers examined genes known to be involved in ion channel formation in muscle. A new gene, KCNJ18, was found to be responsible for forming a newly recognized potassium channel, an inwardly rectifying potassium channel, Kir2.6. Furthermore, its activity is increased by thyroid hormone. Six mutations in KCNJ18 were identified and shown to cause some cases of TPP. The different mutations cause muscle weakness by allowing too much or too little potassium into and out of muscle cells or directing it to the wrong area. The resulting effects on muscle membrane excitability result in the extreme weakness and paralysis experienced by people with TPP. In the study population, the identified mutations were found to be responsible in 25% to 33% of TTP patients from some ethnic groups (Caucasian, Brazilian and Singaporean). No mutations were found in 281 healthy people. Treating hyperthyroidism with anti-thyroid medications usually cures TTP. It can however be difficult to diagnose and early recognition of TPP is vital to initiating appropriate treatment. This research will give clinicians a better understanding of the condition and may lead to diagnostic tests. Further study of this newly recognized channel could lead to new insights into the biology and physiology of muscle, which may ultimately lead to benefits for patients with muscle disease. The newly discovered potassium channel expands scientists’ understanding of the ways in which healthy and diseased muscle works, and potentially could have benefit in a number of other muscle diseases.
Mutations in potassium channel Kir2.6 cause susceptibility to thyrotoxic hypokalemic
periodic paralysis.
Cell. 2010 Jan 8;140(1):88-98.
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