A Late Diagnosis of Andersen-Tawil Syndrome in Teenage Siblings.

BACKGROUND: Andersen-Tawil syndrome (ATS) is a rare autosomal dominant disorder characterized by a classic symptom triad, including periodic paralysis, ventricular arrhythmias with associated prolonged QT interval and U waves, and dysmorphic facial and skeletal features. Pathogenic variants of the KCNJ2 gene are linked to ATS. METHODS: We present two siblings with the same pathogenic mutation and facial characteristic of hypotelorism, yet with intrafamilial and sex-specific variability. RESULTS: The first patient is a 16-year-old male who presented from an outside hospital with subacute-onset weakness. The symptoms almost completely subsided the following day, with only mild proximal muscle weakness. Magnetic resonance imaging of the brain and cervical spine was unremarkable. He had one prior attack of self-resolving weakness without apparent triggering factors and a history of premature ventricular contractions and U waves seen on electrocardiogram without cardiac symptoms. On further evaluation his physical examination was significant for micrognathia, hypotelorism, and clinodactyly. Electrodiagnostic examination showed no clear evidence of polyneuropathy. Given his presentation of the typical triad of periodic weakness, dysmorphic features, and cardiac rhythm abnormalities, genetic testing was pursued revealing a pathogenic mutation of the KCNJ2 gene, indicative of ATS. Subsequent genetic testing of his older biological sister, with identical physical features but without a history of cardiac symptoms or episodic periodic paralysis, revealed the same pathogenic mutation. CONCLUSIONS: It is essential to note that ATS can manifest with a wide range of symptoms and some individuals may display only subtle or atypical signs, contributing to this challenging diagnosis.

Unraveling the Clinical Complexity of Thyrotoxic Periodic Paralysis: A Case Report.

Thyrotoxic periodic paralysis (TPP) is a clinical condition characterized by hypokalemia, muscle paralysis, and hyperthyroidism. TPP can be challenging to diagnose due to its low disease prevalence and the similarity of paralysis to other common conditions. Through this case report, we highlight the importance of considering hyperthyroidism as a cause of recurrent attacks of muscle paralysis, particularly in the setting of other signs of hyperthyroidism. A 32-year-old Hispanic man with a history of recurrent episodes of muscle weakness presented to the hospital with the acute onset of bilateral lower extremity weakness and an inability to ambulate. Additionally, the patient was experiencing symptoms of hyperthyroidism, including heat intolerance, weight loss, anxiety, and tremors. Lab evaluation showed hypokalemia, and the thyroid panel indicated hyperthyroidism due to Graves disease. His symptoms resolved after the replacement of potassium orally and intravenously, and he was discharged home on methimazole and propranolol. The presented case emphasizes that endocrinological and metabolic causes should be considered in the differential diagnosis of acute flaccid paralysis. The symptoms of hyperthyroidism can be subtle in many cases, which can make the diagnosis very challenging.

Pediatric neuromuscular channelopathies.

Pediatric skeletal muscle channelopathies include a spectrum of conditions including nondystrophic myotonias and periodic paralyses. They are rare inherited conditions that can cause significant morbidity. They are characterized by episodic stiffness and weakness. While there is significant phenotypic variability, there are distinct diagnostic features. The nondystrophic myotonias encompass myotonia congenita, paramyotonia congenita, and sodium channel myotonia caused by mutations in chloride and sodium channels. The clinical manifestations vary across age groups and a small subset with sodium channel mutations may have severe presentation with fetal akinesia, laryngospasm, or congenital myopathy. The periodic paralyses include hypokalemic periodic paralysis, hyperkalemic periodic paralysis, and Andersen-Tawil syndrome. The phenotypic differences between the groups can be helpful in diagnosis. It is important to review the cardiac phenotype in Andersen-Tawil syndrome due to a risk of life-threatening cardiac arrhythmias. Early and accurate diagnosis utilizing clinical features aided by investigations is important across all the pediatric channelopathies, as effective symptomatic treatment is available and can substantially improve quality of life.

Andersen-Tawil syndrome.

Andersen-Tawil syndrome (ATS) is one of the periodic paralyses, a set of skeletal muscle disorders that cause transient weakness of the arms and legs lasting minutes to many hours. Distinguishing features of ATS include facial and limb dysmorphisms, cardiac arrhythmia, difficulties with executive function, and association with dominant mutations in the potassium channel, KCNJ2. In this review, we discuss the key features of ATS, diagnostic testing, pathophysiology and treatment of ATS, and compare them with other periodic paralyses.

Thyrotoxic Periodic Paralysis in a Samoan Male With Metabolic Acidosis: A Case Report and Review of the Literature.

Thyrotoxic periodic paralysis (TPP) is a rare disorder characterized by muscle paralysis, thyrotoxicosis, and hypokalemia. It commonly manifests as paralysis of both proximal and distal upper and lower limbs, and if left untreated, may progress to respiratory failure or cardiac arrhythmias. It is most common in Asian males and is frequently precipitated by strenuous exercise, high carbohydrate diet, stress, corticosteroid therapy, or alcohol. Early diagnosis of TPP is crucial as the condition may be reversible with oral or IV potassium replacement therapy, and management of the underlying hyperthyroidism. We describe a Samoan man in his 30s who presented with acute onset lower extremity paralysis. Laboratory investigations revealed low serum potassium of 2.2 mEq/L (reference range 3.5-5.0 mEq/L) and thyrotoxicosis with a low (thyroid stimulating hormone (TSH) of <0.07 uIU/mL (reference range 0.27-4.20 uIU/mL) and an elevated free T4 of 5.4 ng/dL (reference range 0.9-2.1 ng/dL). He was treated with both oral and IV potassium chloride as well as propranolol and regained full strength in his extremities. While rare, TPP is a reversible complication of thyrotoxicosis and a high index of suspicion in clinical practice is essential to prevent adverse outcomes.

Coincident Thyrotoxic Hypokalemic Periodic Paralysis and Cardiomyopathy.

Thyrotoxic periodic paralysis (TPP) and thyrotoxic cardiomyopathy (TCMP) are potentially lethal complications of thyrotoxicosis that require emergent recognition and management to attenuate significant morbidity and mortality. We present the case of a 23-year-old Asian male with no prior medical history who developed TPP with coincident TCMP, which was successfully managed with antithyroid and heart failure therapies. The clinician should be aware of the diagnosis and treatment of these 2 life-threatening conditions in a hyperthyroid state.

Torsade de Pointes Caused by a Compound Licorice Tablet.

The clinical manifestations of licorice-induced pseudoaldosteronism include muscle weakness, periodic paralysis, hypokalemia, and hypertension. Excessive licorice consumption can lead to adverse reactions affecting multiple systems, including the endocrine, cardiovascular, nervous, digestive, and immune systems. Although licorice is a frequently used Chinese herbal medicine, life-threatening adverse reactions have been reported among its users. This article presents a case of severe hypokalemia, torsade de pointes, severe hypertension, and exacerbation of manic symptoms resulting from an overdose of compound licorice tablets. This study aimed to enhance the understanding of the causes of hypokalemia and raise awareness on the potentially fatal adverse reactions associated with licorice drugs.

Convergence of Crisis: A Case Report of Diabetic Ketoacidosis Masking an Impending Thyroid Storm and Periodic Paralysis.

Diabetic ketoacidosis (DKA) is an extreme complication of diabetes mellitus characterized by hyperglycemia, metabolic acidosis, and ketonemia. Thyroid storm, a potentially life-threatening manifestation of thyrotoxicosis, presents with a multitude of symptoms, including hyperthermia, tachycardia, and altered mental status. Periodic paralysis can be precipitated by different metabolic disturbances, including thyrotoxicosis, and may lead to extreme episodes of muscle weakness and paralysis. We present a case of a 41-year-old female with a history of type 1 diabetes mellitus and hyperthyroidism, who presented with DKA complicated by an impending thyroid storm and likely periodic paralysis exacerbated due to hypokalemia. Prompt recognition and aggressive management of each component of this triad were essential for a positive patient outcome. This case highlights the importance of a broad and comprehensive approach to managing complex metabolic emergencies, particularly in patients with multiple comorbidities. Our patient presented to the emergency department with symptoms of severe vomiting, shortness of breath, and altered mental status. Laboratory investigations revealed metabolic derangements consistent with DKA, alongside impending thyrotoxicosis and hypokalemia-induced periodic paralysis. Management involved aggressive fluid resuscitation, insulin therapy, anti-thyroid medications, and potassium supplementation, with a multidisciplinary approach to stabilize the patient's condition.

Anaesthetic management of a parturient with hypokalaemic periodic paralysis for caesarean section: A case report and review of the literature.

A 32-year-old multigravida woman, with known familial hypokalaemic periodic paralysis, underwent spinal anaesthesia for an elective lower segment caesarean section. There are several case reports in the literature discussing the optimal anaesthetic technique. In the past there has not been an emphasis on aggressive and early potassium replacement. A target level to commence replacement of potassium at 4.0 mmol/L or less is proposed. Careful preoperative preparation, frequent perioperative monitoring and early potassium replacement resulted in no perioperative episodes of weakness in this case, in contrast with other case reports where potassium was either not monitored or not replaced early enough, resulting in postoperative attacks. Another factor to consider in hypokalaemic periodic paralysis is the avoidance of triggers, including certain medications. Misoprostol was used in this instance to avoid potential electrolyte derangements from other uterotonics.

Quality of life in hypokalemic periodic paralysis - a survey.

Primary hypokalemic periodic paralysis (HypoPP) is a skeletal muscle channelopathy most commonly caused by pathogenic variants in the calcium channel gene, CACNA1S. HypoPP can present with attacks of paralysis and/or permanent muscle weakness. Previous studies have shown that patients with HypoPP can have impaired quality of life (QoL). In this cross-sectional study, we aimed to describe the QoL in patients with HypoPP caused by pathogenic variants in CACNA1S using The Individualized Neuromuscular Quality of Life (INQoL) questionnaire, a validated tool to measure the QoL of patients with neuromuscular diseases (higher score, worse QoL). We showed that muscle weakness and fatigue were the symptoms with the greatest impact on participants' lives and that "activities", in the life domain of the INQoL, was most affected by HypoPP. Furthermore, we showed that the total INQoL score increased with age. Low QoL was primarily driven by progressive permanent muscle weakness and not attacks of paralysis, although half of the participants reported that attacks of paralysis challenged their daily life. The results suggest that special attention should be given to muscle weakness and fatigue in patients with HypoPP.

Case report: thyrotoxic periodic paralysis, an unusual cause of hypokalemia.

Introduction: Thyrotoxic periodic paralysis (TPP) is a type of hypokalemic periodic paralysis that is caused by an underlying thyrotoxicosis. It is a rare cause of hypokalemia due to intracellular potassium shift, causing acute muscle weakness.Case presentation: We present a case of a 19-year-old male of Thai descent with acute proximal symmetric lower limb weakness. The combination of these symptoms with profound hypokalemia, rapid recovery after normalization of serum potassium, and evidence of hyperthyroidism led to the diagnosis of thyrotoxic periodic paralysis, in this case due to an underlying Graves' disease.Conclusion: Clinicians should consider the diagnosis of TPP when a patient presents with the triad of acute paresis, profound hypokalemia and hyperthyroidism.

Hyperandrogenism and Hypokalemic Thyrotoxic Periodic Paralysis in a North American Adolescent Girl.

We present a unique case of hypokalemic thyrotoxic periodic paralysis (TPP) in an adolescent girl in North America. TPP is a rare but dangerous complication seen in thyrotoxic patients characterized by hypokalemia and acute proximal symmetric lower-extremity weakness. It is an especially rare phenomenon in pediatrics, with roughly 20 case reports described in adolescents worldwide; the majority are male. Our patient is a 14-year-old Asian girl with biochemical hyperandrogenism and known Graves disease who presented with an acute episode of lower-extremity weakness after eating a carbohydrate-rich meal. Laboratory workup revealed hypokalemia, hypomagnesemia, an undetectable thyrotropin, and hyperthyroxinemia. Electrolyte derangements responded well to supplementation, and the muscle weakness resolved with electrolyte normalization. Following improvement in thyroid function, the patient underwent thyroidectomy for definitive management of Graves disease. As TPP is potentially exacerbated by higher androgen and insulin levels, we suspect that with increasing rates of obesity and polycystic ovary syndrome, the incidence of TPP among adolescents may increase. It is therefore critically important that there is awareness and recognition of this serious diagnosis among all health care providers.

Hyperkalemic Periodic Paralysis Secondary to End-Stage Renal Disease and Excess Potato Consumption.

Hyperkalemic periodic paralysis is a rare medical condition characterized by periods of extreme muscle weakness or paralysis. While most cases of hyperkalemic periodic paralysis are associated with a genetic channelopathy, cases of secondary hyperkalemic periodic paralysis can pose a challenge for medical personnel in terms of timely recognition. Identification of this medical emergency early in its course is essential to preventing cardiac and neurological sequelae. We report a case of a 58-year-old female who presented with stroke-like symptoms and was found to have secondary hyperkalemic periodic paralysis attributed to the excess consumption of potatoes, a potassium-rich food. This case highlights the importance of considering hyperkalemic periodic paralysis early in the differentiation of patients with end-stage renal disease (ESRD) who present with muscle weakness and stroke-like symptoms.

Atypical Normokalemic Case of Thyrotoxic Periodic Paralysis in a Pediatric Patient.

Thyrotoxic periodic paralysis (TPP) is a rare complication of hyperthyroidism characterized by typical muscular symptoms, ranging from paresis to complete paralysis, commonly associated with low potassium blood levels (<3 mmol/l). It is more commonly reported in adult Asian individuals and can lead to life-threatening situations. Therefore, early clinical diagnosis and targeted therapy are of crucial importance. In this article, we report the case of a 17-year-old adolescent with a Vietnamese background and known Graves' disease who was admitted with typical TPP-related symptoms but no hypokalemia. After treatment with an antithyroid medication and oral potassium supplementation, no new episode of TPP was observed. Using next-generation sequencing, a genetic analysis of TPP-related ion channel genes (KCNJ2, KCNJ18, KCNE3, SCN4A, and CACNA1S) found no known/likely pathogenic variants or variants of unknown significance. To the best of our knowledge, this is only the second reported case of quite normokalemic TPP in the pediatric population. Prompt diagnosis of TPP is essential to prevent harmful complications. Supplementation with potassium appears to be successful alongside non-selective beta-blockers. Normalization of thyroid function should be pursued to prevent new attacks, which is considered the best preventive measure.

Diagnosis, management and outcomes of primary hypokalemic periodic paralysis during pregnancy.

Primary hypokalaemic periodic paralysis during pregnancy has been rarely reported. Four pregnant women with the acute onset of flaccid paralysis presented between January 2018 and December 2021. Focussed history and physical examination helped an appropriate radiological and laboratory investigation plan to be made. All women recovered within 4-7 days of potassium supplementation. Supplemental potassium continued until delivery. A pain management plan with continuous epidural infusion helped in avoiding stress-induced hypokalaemia. None of the women developed an episode of muscle weakness during the intervening period. In conclusion, a focussed history and targeted laboratory investigation are needed to diagnose primary hypokalaemic periodic paralysis. Early administration of oral or intravenous potassium is crucial in improving fetomaternal outcomes.

Genetic analysis of 37 cases with primary periodic paralysis in Chinese patients.

BACKGROUND: Primary periodic paralysis (PPP) is an inherited disorders of ion channel dysfunction characterized by recurrent episodes of flaccid muscle weakness, which can classified as hypokalemic (HypoPP), normokalemic (NormoPP), or hyperkalemic (HyperPP) according to the potassium level during the paralytic attacks. However, PPP is charactered by remarkable clinical and genetic heterogeneity, and the diagnosis of suspected patients is based on the characteristic clinical presentation then confirmed by genetic testing. At present, there are only limited cohort studies on PPP in the Chinese population. RESULTS: We included 37 patients with a clinical diagnosis of PPP. Eleven (29.7%) patients were tested using a specific gene panel and 26 (70.3%) by the whole-exome sequencing (WES). Twenty-two cases had a genetic variant identified, representing a diagnostic rate of 59.5% (22/37). All the identified mutations were either in the SCN4A or the CACNA1S gene. The overall detection rate was comparable between the panel (54.5%: 6/11) and WES (61.5%: 16/26). The remaining patients unresolved through panel sequencing were further analyzed by WES, without the detection of any mutation. The novel atypical splicing variant c.2020-5G > A affects the normal splicing of the SCN4A mRNA, which was confirmed by minigene splicing assay. Among 21 patients with HypoPP, 15 patients were classified as HypoPP-2 with SCN4A variants, and 6 HypoPP-1 patients had CACNA1S variants. CONCLUSIONS: Our results suggest that SCN4A alleles are the main cause in our cohort, with the remainder caused by CACNA1S alleles, which are the predominant cause in Europe and the United States. Additionally, this study identified 3 novel SCN4A and 2 novel CACNA1S variants, broadening the mutation spectrum of genes associated with PPP.

Case report: Dihydropyridine receptor (CACNA1S) congenital myopathy, a novel phenotype with early onset periodic paralysis.

Introduction: CACNA1S related congenital myopathy is an emerging recently described entity. In this report we describe 2 sisters with mutations in the CACNA1S gene and the novel phenotype of congenital myopathy and infantile onset episodic weakness. Clinical description: Both sisters had neonatal onset hypotonia, muscle weakness, and delayed walking. Episodic weakness started in infancy and continued thereafter, provoked mostly by cold exposure. Muscle imaging revealed fat replacement of gluteus maximus muscles. Next generation sequencing found the missense p.Cys944Tyr variant and the novel splicing variant c.3526-2A>G in CACNA1S. Minigene assay revealed the splicing variant caused skipping of exon 28 from the transcript, potentially affecting protein folding and/or voltage dependent activation. Conclusion: This novel phenotype supports the notion that there are age related differences in the clinical expression of CACNA1S gene mutations. This expands our understanding of mutations located in regions of the CACNA1S outside the highly conserved S4 segment, where most mutations thus far have been identified.

Recurrent Thyrotoxic Periodic Paralysis As the Sole Clinical Manifestation of Untreated Hyperthyroidism.

Thyrotoxic periodic paralysis (TPP) is a complication of hyperthyroidism that predominantly affects the Asian population. Episodes of muscle paralysis typically coincide with symptoms of hyperthyroidism. However, we present a unique case of TPP in a 32-year-old African American patient where TPP served as the primary manifestation of thyrotoxicosis. The patient was discharged with a resolution of symptoms after correcting electrolyte abnormalities.

Physiotherapy Strategies in Hypokalemic Periodic Paralysis: A Case Report.

The rare neuromuscular disease known as hypokalemic periodic paralysis (hypoKPP), which results in severe muscle weakness in the extremities, is brought on by abnormalities in potassium transport within cells. Laboratory testing is confirmatory, which reveals notably low potassium levels, causing paralysis, which improves once the low potassium is restored. The patient generally complains of muscle weakness with difficulty in performing activities of daily living and impaired participation in functional tasks, with few suffering from coexisting sensory impairments. Physiotherapy generally plays a symptomatic role with motion exercises for the affected muscle groups. There is no standardized physiotherapy protocol for disease-specific impairments. A 46-year-old man complained of bilateral upper and lower limb muscular weakness and was admitted to the neurology ward. The patient also complained of having tingling numbness throughout their entire limbs and had experienced similar episodes of symptoms six months prior. During laboratory evaluation, a significantly low potassium level was found, leading to a diagnosis of hypoKPP. Following medical management, neurophysiotherapy was initiated. Physiotherapy strategy shows significant improvement in muscular strength and functional activities. Thus, this case report concludes that physiotherapy plays a vital role in managing hypoKPP by enhancing muscular strength, functional activities, and quality of life.

Hypokalemic Periodic Paralysis Type 2 Due to SCN4A Val1105Met Mutation: A Case Study.

Hypokalemic Periodic Paralysis Type 2 (HOKPP2) is a rare autosomal dominant disorder characterized by recurrent episodes of muscle weakness, paralysis, and hypokalemia. In this case report, we present the clinical details of a 49-year-old female diagnosed with HOKPP2. Genetic testing revealed a heterozygous mutation in the Sodium Voltage-Gated Channel Alpha Subunit 4 (SCN4A) gene, confirming the diagnosis of HOKPP2. Management strategies, including potassium supplementation and lifestyle modifications, were implemented, resulting in a significant decrease in the frequency of symptomatic episodes. This case highlights the importance of considering HOKPP2 in patients with recurrent muscle weakness, particularly those with a familial history of similar symptoms. Furthermore, it underscores the crucial role of genetic testing in guiding patient management and facilitating genetic counseling.