About Mikhail Sinelnikov
Mikhail joined SpringerNature in 2023 and is the editor for BMC Nephrology, BMC Surgery and BMC Urology. He is a Doctor of Medicine with clinical experience centered in oncology and reconstructive surgery, as well as academic experience in anatomy, physiology and histology. After completing residency, he obtained a double PhD in Regenerative Medicine and Surgical Oncology. In line with his clinical and academic work, he led several research projects in the field of regenerative medicine, including a postdoctoral position at Mayo Clinic. Mikhail is passionate about accessibility and transparency in research, both principles upheld by BMC Series journals. His goal as an editor is to promote these principles of open access to help authors maximize the impact of their research and reach a rapidly growing audience.
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The correct answer is explained below:
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The correct answer is: hypokalemic periodic paralysis.
Periodic paralysis (PP) is a rare channelopathy marked by recurrent episodes of flaccid skeletal muscle paralysis. Hypokalemic periodic paralysis (HypoPP) is categorized into familial or acquired forms. Triggers for episodes of HypoPP are primarily associated with intense exercise and high carbohydrate intake, and less frequently related to viral infections, stress, cold, salt consumption, and medications (such as glucocorticoids and insulin).
Familial HypoPP is associated with variants in the skeletal muscle sodium channel gene SCN4A in 20% of patients or the L-type calcium channel gene CACNA1S in 60% of patients. The majority of reported pathogenic variants involve arginine residues in S4 transmembrane segments, with notable hotspots at codons R528 and R1239. Generally, the existence of hyperthyroidism is more strongly associated with a diagnosis of acquired thyrotoxic periodic paralysis (TPP), with most cases occurring in Asian males without a family history of the condition. Pathogenic variants in KCNJ2 and KCNJ18 are associated with susceptibility to TPP. KCNJ2 and KCNJ18 encode Kir 2.1 and Kir2.6 respectively, inwardly rectifying potassium channels expressed in skeletal muscle and transcriptionally regulated by thyroid hormone.
Genetic testing in the discussed patient revealed a heterozygous pathogenic variant in CACNA1S [c.1583 G>A (p. R528H)] and normal sequencing of SCN4A, KCNJ2 and KCNJ18. The patient received a diagnosis of familial hypokalemic periodic paralysis and concurrent hyperthyroidism due to Graves’ disease. The likelihood of TPP in this case is reduced, given the patient is not of Asian descent, has a family history of HypoPP, and lacks identifiable variants in KCNJ2 and KCNJ18. The pathogenic variant observed in this case has been documented previously. This variant leads to a substantial reduction in the whole-cell calcium channel current and induces depolarization of the resting cell potential in response to hypokalemia.
Management of acute paralytic episodes involves maintaining proper control of serum potassium levels, necessitating vigilant monitoring for post-treatment hyperkalemia. Lifestyle and dietary modifications to avoid triggering factors are integral to treatment. Although the precise mechanism is not fully elucidated, carbonic anhydrase inhibitors have demonstrated efficacy in reducing the frequency of familiar HypoPP episodes. There is variability in the response to carbonic anhydrase inhibitors based on genotype; individuals with CACNA1S variants tend to exhibit a more favorable response compared to SCN4A variants. Additionally, the incorporation of a potassium-sparing diuretic, either in conjunction with carbonic anhydrase inhibitors or as a standalone treatment, may offer advantages for specific patients.
Read more in the published article: https://bmcnephrol.biomedcentral.com/articles/10.1186/s12882-024-03749-x
Read more in the published article: https://bmcnephrol.biomedcentral.com/articles/10.1186/s12882-024-03749-x
The correct answer is explained below:
.
.
.
.
.
The correct answer is: hypokalemic periodic paralysis.
Periodic paralysis (PP) is a rare channelopathy marked by recurrent episodes of flaccid skeletal muscle paralysis. Hypokalemic periodic paralysis (HypoPP) is categorized into familial or acquired forms. Triggers for episodes of HypoPP are primarily associated with intense exercise and high carbohydrate intake, and less frequently related to viral infections, stress, cold, salt consumption, and medications (such as glucocorticoids and insulin).
Familial HypoPP is associated with variants in the skeletal muscle sodium channel gene SCN4A in 20% of patients or the L-type calcium channel gene CACNA1S in 60% of patients. The majority of reported pathogenic variants involve arginine residues in S4 transmembrane segments, with notable hotspots at codons R528 and R1239. Generally, the existence of hyperthyroidism is more strongly associated with a diagnosis of acquired thyrotoxic periodic paralysis (TPP), with most cases occurring in Asian males without a family history of the condition. Pathogenic variants in KCNJ2 and KCNJ18 are associated with susceptibility to TPP. KCNJ2 and KCNJ18 encode Kir 2.1 and Kir2.6 respectively, inwardly rectifying potassium channels expressed in skeletal muscle and transcriptionally regulated by thyroid hormone.
Genetic testing in the discussed patient revealed a heterozygous pathogenic variant in CACNA1S [c.1583 G>A (p. R528H)] and normal sequencing of SCN4A, KCNJ2 and KCNJ18. The patient received a diagnosis of familial hypokalemic periodic paralysis and concurrent hyperthyroidism due to Graves’ disease. The likelihood of TPP in this case is reduced, given the patient is not of Asian descent, has a family history of HypoPP, and lacks identifiable variants in KCNJ2 and KCNJ18. The pathogenic variant observed in this case has been documented previously. This variant leads to a substantial reduction in the whole-cell calcium channel current and induces depolarization of the resting cell potential in response to hypokalemia.
Management of acute paralytic episodes involves maintaining proper control of serum potassium levels, necessitating vigilant monitoring for post-treatment hyperkalemia. Lifestyle and dietary modifications to avoid triggering factors are integral to treatment. Although the precise mechanism is not fully elucidated, carbonic anhydrase inhibitors have demonstrated efficacy in reducing the frequency of familiar HypoPP episodes. There is variability in the response to carbonic anhydrase inhibitors based on genotype; individuals with CACNA1S variants tend to exhibit a more favorable response compared to SCN4A variants. Additionally, the incorporation of a potassium-sparing diuretic, either in conjunction with carbonic anhydrase inhibitors or as a standalone treatment, may offer advantages for specific patients.
Read more in the published article: https://bmcnephrol.biomedcentral.com/articles/10.1186/s12882-024-03749-x