Phospholemman, a major regulator of skeletal muscle Na+/K+-ATPase, is not mutated in probands with hypokalemic periodic paralysis.

The pathogenesis of hypokalemic periodic paralysis (HypoPP) remains unclear. Though some mutations in skeletal muscle ion channels were revealed previously, the exact mechanism remains to be fully elucidated. Increased Na+/K+-ATPase activity in skeletal muscle is postulated to contribute to attacks of HypoPP. Before the link between Na+/K+-ATPase dysfunction and these ion channel mutations is established, mutations in Na+/K+-ATPase and their regulators are the first to be excluded. Phospholemman, which is a protein encoded by the FXYD domain-containing ion transport regulator 1 (FXYD1) gene, is predominantly expressed in skeletal muscle and is the major regulator of Na+/K+-ATPase. Therefore, the aim of the present study was to determine the genetic involvement of phospholemman in HypoPP development. Genomic DNA was extracted from the peripheral blood of five HypoPP probands with typical manifestations. The coding exons of FXYD1, exons 2-7, were polymerase chain reaction (PCR)-amplified and sequenced. No mutations were detected in FXYD1 in any of the subjects studied. To conclude, mutations in phospholemman encoding genes may not be involved with HypoPP and the relationship between phospholemman and Na+/K+-ATPase dysfunction in attacks of HypoPP requires further study.

Mutation analysis of CACNA1S and SCN4A in patients with hypokalemic periodic paralysis.

Mutations in CACNA1S (calcium channel, voltage­dependent, L type, alpha 1S subunit) and SCN4A (sodium channel, voltage­gated, type IV, alpha subunit) are associated with hypokalemic periodic paralysis (HPP). The aim of the current study was to investigate CACNA1S and SCN4A mutations in patients with HPP. Mutations in CACNA1S and SCN4A were detected in three familial hypokalemic periodic paralysis (FHPP) pedigrees and in two thyrotoxic hypokalemic periodic paralysis (THPP) pedigrees using polymerase chain reaction, DNA sequencing and sequence alignment with GenBank data. A single base mutation from cytosine to guanine at site 1582 was identified in exon 11 of CACNA1S in one FHPP pedigree, resulting in an arginine to glycine (R528G) substitution. A single base mutation from thymine to cytosine at site 2012 was identified in exon 12 of SCN4A in one THPP pedigree, resulting in a phenylalanine to serine (F671S) substitution. No mutations in CACNA1S or SCN4A were identified in the remaining three pedigrees. The present study indicated that CACNA1S and SCN4A mutations are relatively rare in patients with HPP, and further studies are required to determine whether these mutation­associated substitutions are representative of patients with HPP.

Painful neuropathy in a diabetic patient resulting from lung cancer and not diabetes: A case report.

The current study reports the case of a 61-year-old man with diabetes who was suffering from generalized pain over the whole body and gradually progressive numbness. The patient was initially diagnosed with diabetic peripheral neuropathy and received treatment, however, the symptoms persisted. In October 2010, the patient was admitted to the Chinese People's Liberation Army Navy General Hospital (Beijing, China) for the treatment of diabetes, however, a full-body sharp pain was also described, which was relieved upon massaging the area. Causes, other than diabetes, were investigated for these symptoms. Chest computed tomography and positron emission tomography-computed tomography scans revealed a mass shadow in the right lower lobe of the lung, with multiple lymphatic metastases. Lung cancer was diagnosed with a tumor-node-metastasis stage of T1N3Mx. Following treatment of the cancer with chemotherapy and radiotherapy, the patient's symptoms were significantly improved. The present study reports a rare case of a paraneoplastic neurological syndrome (PNS) that presented as painful neuropathy resulting from lung cancer, which mimicked diabetic peripheral neuropathy.