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Case report: A novel CACNA1S mutation associated with hypokalemic periodic paralysis.

ABSTRACT:

Background

Hypokalemic periodic paralysis (HypoKPP) is a rare neuromuscular genetic disorder causing recurrent episodes of flaccid paralysis. Most cases are associated with CACNA1S mutation, causing defect of calcium channel and subsequent impairment of muscle functions. Due to defined management approaches early diagnosis is crucial for promptly treatment and prevention new attacks.

Materials and methods

We report a case of HypoKPP associated with previously unreported mutation in CACNA1S gene (p.R900M). Molecular modeling of Ca_V1.1 was applied to evaluate its pathogenicity.

Results

As a patient referred between attacks neurological status, laboratory and neurophysiological examination were unremarkable. Molecular modeling predicted that the p.R900M mutation affects the process of calcium channels activation.

Conclusion

Novel CACNA1S mutation, associated with HypoKPP was identified. Monte-Carlo energy minimization of the Ca_V1.1 model supported the association of this mutation with this disease.

SUBMITTER: Nuzhnyi EP

PROVIDER: S-EPMC10570449 | biostudies-literature | 2023

REPOSITORIES: biostudies-literature

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Case report: A novel <i>CACNA1S</i> mutation associated with hypokalemic periodic paralysis.

Nuzhnyi Evgenii P EP Arestova Alina S AS Rossokhin Alexey V AV Protopopova Anna O AO Abramycheva Nataliya Yu NY Suponeva Natalia A NA Illarioshkin Sergey N SN

Frontiers in neurology 20230929

<h4>Background</h4>Hypokalemic periodic paralysis (HypoKPP) is a rare neuromuscular genetic disorder causing recurrent episodes of flaccid paralysis. Most cases are associated with <i>CACNA1S</i> mutation, causing defect of calcium channel and subsequent impairment of muscle functions. Due to defined management approaches early diagnosis is crucial for promptly treatment and prevention new attacks.<h4>Materials and methods</h4>We report a case of HypoKPP associated with previously unreported mut ...[more]

PMID: 37840943

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Project description:BackgroundHypokalemic periodic paralysis is a rare neuromuscular genetic disorder due to defect of ion channels and subsequent function impairment. It belongs to a periodic paralyses group including hyperkalemic periodic paralysis (HEKPP), hypokalemic periodic paralysis (HOKPP) and Andersen-Tawil syndrome (ATS). Clinical presentations are mostly characterized by episodes of flaccid generalized weakness with transient hypo- or hyperkalemia.Case presentationA teenage boy presented to Emergency Department (ED) for acute weakness and no story of neurological disease, during the anamnestic interview he revealed that he had a carbohydrates-rich meal the previous evening. Through a focused diagnostic work-up the most frequent and dangerous causes of paralysis were excluded, but low serum potassium concentration and positive family history for periodic paralyses raised the diagnostic suspicion of HOKPP. After the acute management in ED, he was admitted to Pediatric Department where a potassium integration was started and the patient was counselled about avoiding daily life triggers. He was discharged in few days. Unfortunately, he presented again because of a new paralytic attack due to a sugar-rich food binge the previous evening. Again, he was admitted and treated by potassium integration. This time he was strongly made aware of the risks he may face in case of poor adherence to therapy or behavioral rules. Currently, after 15 months, the boy is fine and no new flare-ups are reported.ConclusionHOKPP is a rare disease but symptoms can have a remarkable impact on patients' quality of life and can interfere with employment and educational opportunities. The treatment aims to minimize the paralysis attacks by restoring normal potassium level in order to reduce muscle excitability but it seems clear that a strong education of the patient about identification and avoidance triggering factors is essential to guarantee a benign clinical course. In our work we discuss the typical clinical presentation of these patients focusing on the key points of the diagnosis and on the challenges of therapeutic management especially in adolescence. A brief discussion of the most recent knowledge regarding this clinical condition follows.

Project description:BackgroundAcute hypokalaemic paralysis is characterised by acute flaccid muscle weakness and has a complex aetiological spectrum. Herein we report, for the first time, a case of unilateral adrenal hyperplasia accompanied by hypokalaemic periodic paralysis type I resulting from a novel dominant mutation in CACNA1S. We present the clinical features and prognosis after adrenalectomy in this case.Case presentationA 43-year-old Han Chinese male presented with severe hypokalaemic paralysis that remitted after taking oral potassium. The patient had suffered from periodic attacks of hypokalaemic paralysis for more than 20 years. A computed tomography (CT) scan of the abdomen showed a nodular mass on the left adrenal gland, although laboratory examination revealed the patient had not developed primary aldosteronism. The patient underwent a left adrenalectomy 4 days after admission, and the pathological examination further confirmed a 1.1 cm benign nodule at the periphery of the adrenal gland. Three months after the adrenalectomy, a paralytic attack recurred and the patient asked for assistance from the Department of Medical Genetics. His family history showed that two uncles, one brother, and a nephew also had a history of periodic paralysis, although their symptoms were milder. The patient's CACNA1S and SCN4A genes were sequenced, and a novel missense mutation, c.1582C > T (p.Arg528Cys), in CACNA1S was detected. Detection of the mutation in five adult male family members, including three with periodic paralysis and two with no history of the disease, indicated that this mutation caused hypokalaemic periodic paralysis type I in his family. Follow-up 2 years after adrenalectomy showed that the serum potassium concentration was increased between paralyses and the number and severity of paralytic attacks were significantly decreased.ConclusionWe identified a novel dominant mutation, c.1582C > T (p.Arg528Cys), in CACNA1S that causes hypokalaemic periodic paralysis. The therapeutic effect of adrenalectomy indicated that unilateral adrenal hyperplasia might make paralytic attacks more serious and more frequent by decreasing serum potassium. This finding suggests that the surgical removal of hyperplastic tissues might relieve the symptoms of patients with severe hypokalaemic paralysis caused by other incurable diseases, even if the adrenal lesion does not cause primary aldosteronism.