Prevalence and risk factors of low vitamin D levels in children and adolescents with familial hypokalemic periodic paralysis.

Patients with familial hypokalemic periodic paralysis (HOKPP) experience episodes of reversible immobility and are at an increased risk of limited sunlight exposure, potentially leading to vitamin D deficiency. However, there is a lack of data on vitamin D levels in this population. We investigated serum vitamin D levels and their associated factors in children with HOKPP. This study included 170 genetically-confirmed children with HOKPP, aged 3-18 years, and 170 age-, sex-, and body mass index (BMI)-matched healthy controls from the Korean Channelopathy Study, a prospective controlled investigation. Anthropometric and clinical characteristics were recorded, and serum levels of calcium, ionized calcium, phosphorus, alkaline phosphatase, 25-hydroxyvitamin D, and intact parathyroid hormone (PTH) were analyzed. Vitamin D deficiency (< 20 ng/mL) was observed in 87.0% of the patients compared to 45.5% of the controls (P < 0.05) during the summer-fall season. During the winter-spring season, 91.7% of the patients and 73.4% of the controls were deficient (P < 0.05). A strong positive correlation was found between onset age of the first paralytic attack and vitamin D levels (r = 0.78, P < 0.01). Conversely, the frequency and duration of paralytic attacks were negatively correlated with vitamin D levels (r = -0.82 and r = -0.65, P < 0.01, respectively). Age, BMI, age at onset, frequency and duration of attacks, and PTH levels were independently associated with vitamin D levels (ß = -0.10, -0.12, 0.19, -0.27, -0.21, and -0.13, P < 0.05, respectively). CONCLUSIONS: Vitamin D deficiency was highly prevalent in children with HOKPP, and vitamin D levels correlated with various disease characteristics. We recommend routine screening for vitamin D levels in these patients to address this prevalent deficiency. Considering the high prevalence of vitamin D deficiency observed, further research on other diseases characterized by reversible immobility is warranted. WHAT IS KNOWN: • A correlation between immobility and low serum vitamin D levels has been established. However, the vitamin D status of patients with familial hypokalemic periodic paralysis (HOKPP) who experience periods of reversible immobility remains unknown. WHAT IS NEW: • Vitamin D deficiency was highly prevalent in children with HOKPP, and vitamin D levels correlated with various disease characteristics.

A novel CACNA1S gene variant in a child with hypokalemic periodic paralysis: a case report and literature review.

BACKGROUND: The CACNA1S gene encodes the alpha 1 S-subunit of the voltage-gated calcium channel, which is primarily expressed in the skeletal muscle cells. Pathogenic variants of CACNA1S can cause hypokalemic periodic paralysis (HypoPP), malignant hyperthermia susceptibility, and congenital myopathy. We aimed to study the clinical and molecular features of a male child with a CACNA1S variant and depict the molecular sub-regional characteristics of different phenotypes associated with CACNA1S variants. CASE PRESENTATION: We presented a case of HypoPP with recurrent muscle weakness and hypokalemia. Genetic analyses of the family members revealed that the proband had a novel c.497 C > A (p.Ala166Asp) variant of CACNA1S, which was inherited from his father. The diagnosis of HypoPP was established in the proband as he met the consensus diagnostic criteria. The patient and his parents were informed to avoid the classical triggers of HypoPP. The attacks of the patient are prevented by lifestyle changes and nutritional counseling. We also showed the molecular sub-regional location of the variants of CACNA1S which was associated with different phenotypes. CONCLUSIONS: Our results identified a new variant of CACNA1S and expanded the spectrum of variants associated with HypoPP. Early genetic diagnosis can help avoid diagnostic delays, perform genetic counseling, provide proper treatment, and reduce morbidity and mortality.

Thyrotoxic periodic paralysis associated with lactic metabolic acidosis: Case report of an African man and review of literature.

BACKGROUND: Thyrotoxic periodic paralysis (TPP) is a rare and most often acquired subtype of hypokalemic periodic paralysis. The association of varying degrees of muscle weakness, hyperthyroidism and hypokalemia characterizes it. The treatment requires potassium supplementation, control of hyperthyroidism and prevention measures. It is a frequent disease in Asian men, but much rare in Caucasian or African populations. This is the first report of TPP associated with lactic metabolic acidosis in an African man. CASE PRESENTATION: A 23 year-old African man, native from Morocco, with recurrent episodes of tetraparesis for eleven months, and abdominal pain, was referred for evaluation. Biochemical investigations showed severe hypokalemia associated with hyperthyroidism and lactic metabolic acidosis. His EKG showed signs of hypokalemia such as sinus tachycardia and U waves. After potassium supplementation, neurological recuperation was quick and complete. Thyroid ultrasound identified a hypoechogenic and hypervascularized goiter, associated with high levels of thyroid antibodies, in favor of Grave's disease. With antithyroid drugs and life-style changes, the patient did not have any other attack. REVIEW OF LITERATURE: In addition to the case report, this article presents an extended review of literature, from the first large study reporting the diagnosis and incidence of TPP in 1957 to nowadays. Are reported here the latest information concerning epidemiology, clinical manifestations, complementary examinations, management and genetic finding. The lactic acidosis observed initially is exceptional, never described in TPP. TPP is a diagnostic and therapeutic emergency, requiring careful potassium supplementation, in order to avoid the risk of the onset of rebound hyperkalemia, to be maintained until the etiological treatment is effective. Paraclinical assessment with emergency EKG and electromyogram are essential to assess the impact. DISCUSSION: It is essential in the face of any hypokalaemic periodic paralysis, including in non-Asian subjects, to search hyperthyroidism. CONCLUSIONS: This report demonstrates the importance of thyroid testing in case of acute muscle weakness, even in non-Asian patients in order to diagnose TPP. This is a rare but possible etiology, to be distinguished from the familial form of hypokalemic periodic paralysis. It also questions on the impact of TPP on energetic metabolism, in particular on lactic metabolism.

Childbirth with epidural analgesia in a pregnant woman with hypokalemic periodic paralysis.

Familial hypokalaemic periodic paralysis (FHPP) is an uncommon genetic disease characterized by muscle weakness associated with hypokalaemia. Episodes are precipitated by drugs, stress, metabolic diseases, hypothermia or infection. We report the case of a 38-year-old pregnant women with FHPP who underwent epidural analgesia for labour. Pregnant women with FHPP require multidisciplinary management involving an anaesthesiologist, a gynaecologist and a paediatrician. It is important to maintain normothermia, prevent hyperventilation, monitor electrolytes, avoid glucose infusions and medications that cause hypokalaemia, and administer potassium supplements when required. Locoregional techniques should be preferred over general anaesthesia. Early epidural analgesia reduces the risk of pain that could trigger an episode of FHPP. In the case of general anaesthesia, drugs that can cause malignant hyperthermia should be avoided, and short-acting non-depolarizing neuromuscular blockers with blockade-depth monitoring should be used.

Anaesthesia challenges of a parturient with paramyotonia congenita and terminal filum lipoma presenting for labour and caesarean section under epidural anaesthesia - a case report.

BACKGROUND: Paramyotonia congenita is a rare autosomal dominant myopathy which presents with periodic weakness due to cold and exercise. It is caused by mutations of the SCN4 gene which encodes the sodium channel in skeletal muscles. CASE PRESENTATION: We report a full term obstetric patient with both paramyotonia congenita and terminal filum lipoma who presents for induction of labour followed by an emergency caesarean section performed under epidural anesthesia. Her recovery is subsequently complicated by a 3-day history of postpartum paraparesis attributed to hypokalemic periodic paralysis. CONCLUSION: We describe the perioperative anesthesia considerations and challenges in this case with a review of the current literature. This case report highlights the importance of early proactive and collaborative multidisciplinary approach, maintaining normal temperature and electrolytes with a heightened vigilance for muscle-related perioperative complications.

Permanent muscle weakness in hypokalemic periodic paralysis.

OBJECTIVE: To map the phenotypic spectrum in 55 individuals with mutations in CACNA1S known to cause hypokalemic periodic paralysis (HypoPP) using medical history, muscle strength testing, and muscle MRI. METHODS: Adults with a mutation in CACNA1S known to cause HypoPP were included. Medical history was obtained. Muscle strength and MRI assessments were performed. RESULTS: Fifty-five persons were included. Three patients presented with permanent muscle weakness and never attacks of paralysis. Seventeen patients presented with a mixed phenotype of periodic paralysis and permanent weakness. Thirty-one patients presented with the classical phenotype of periodic attacks of paralysis and no permanent weakness. Four participants were asymptomatic. Different phenotypes were present in 9 of 18 families. All patients with permanent weakness had abnormal replacement of muscle by fat on MRI. In addition, 20 of 35 participants with no permanent weakness had abnormal fat replacement of muscle on MRI. The most severely affected muscles were the paraspinal muscles, psoas, iliacus, the posterior muscles of the thigh and gastrocnemius, and soleus of the calf. Age was associated with permanent weakness and correlated with severity of weakness and fat replacement of muscle on MRI. CONCLUSIONS: Our results show that phenotype in individuals with HypoPP-causing mutations in CACNA1S varies from asymptomatic to periodic paralysis with or without permanent muscle weakness or permanent weakness as sole presenting picture. Variable phenotypes are found within families. Muscle MRI reveals fat replacement in patients with no permanent muscle weakness, suggesting a convergence of phenotype towards a fixed myopathy with aging.

Myotonia congenita and periodic hypokalemia paralysis in a consanguineous marriage pedigree: Coexistence of a novel CLCN1 mutation and an SCN4A mutation.

Myotonia congenita and hypokalemic periodic paralysis type 2 are both rare genetic channelopathies caused by mutations in the CLCN1 gene encoding voltage-gated chloride channel CLC-1 and the SCN4A gene encoding voltage-gated sodium channel Nav1.4. The patients with concomitant mutations in both genes manifested different unique symptoms from mutations in these genes separately. Here, we describe a patient with myotonia and periodic paralysis in a consanguineous marriage pedigree. By using whole-exome sequencing, a novel F306S variant in the CLCN1 gene and a known R222W mutation in the SCN4A gene were identified in the pedigree. Patch clamp analysis revealed that the F306S mutant reduced the opening probability of CLC-1 and chloride conductance. Our study expanded the CLCN1 mutation database. We emphasized the value of whole-exome sequencing for differential diagnosis in atypical myotonic patients.

33-year-old man • flaccid paralysis in limbs • 30-lb weight loss • thyromegaly without nodules • Dx?

Flaccid paralysis in arms and legs. 30-lb weight loss in previous month. Thyromegaly without nodules. Dx?

Coexistence of myasthenia gravis with hypokalemic periodic paralysis: a rare presentation.

Bilateral symmetrical weakness of acute onset is not very uncommon and the differential varies widely from life-threatening neurological illnesses to metabolic and electrolyte derangements. We report the case of a young female with severe muscle weakness, respiratory distress and hypokalemia who required immediate intubation on arrival to emergency department. During hospital course, even after normalisation of serum potassium and some improvement in limb weakness, patient failed multiple attempts of extubation because of type II respiratory failure. Subsequently, acetyl cholinesterase antibodies were checked which came out positive, and diagnosis of myasthenia gravis and hypokalemic periodic paralysis was made. She was successfully extubated after intravenous pulse steroids, pyridostigmine and plasmapheresis. Patient was finally discharged home on oral steroids, pyridostigmine and azathioprine. In a patient presenting with hypokalemic weakness, the suspicion of a second disorder should be very high if weakness fails to resolve following correction of hypokalemia.

Secondary hypokalemic paralysis with bulbar weakness and reversible electrophysiologic abnormalities: A case report and systematic review.

Hypokalemic periodic paralysis secondary to distal renal tubular acidosis presenting with prominent bulbar symptoms is extremely rare. The exact pathophysiology by which hypokalemia causes weakness is yet to be elucidated though muscle and nerve membrane hyperpolarization have been hypothesized. The pathophysiology of bulbar involvement in this condition is even more unclear. We report a case presenting as acute flaccid quadriplegia with prominent bulbar symptoms that reversed once potassium levels returned to normal. Serial nerve conduction studies were performed at various potassium levels revealing electrophysiologic abnormalities that corrected with potassium repletion. A systematic review of the literature was also conducted focusing on bulbar symptoms and electrophysiologic findings in hypokalemic periodic paralysis. Nerve conduction abnormalities in this condition are seldom documented, but reports have shown reduced amplitudes of compound motor action potentials and abnormal F-waves during acute attacks of hypokalemic paralysis.

Thyrotoxic periodic paralysis with ventricular tachycardia.

A 47-year-old man presented to our emergency department (ED) with limbs weakness for 2 h. His heart rate was 127 beats per minute and blood pressure was 95/49 mm Hg. He found weakness of limbs after 4-h sleep. Physical examinations revealed that the muscle strength of upper limbs is 3/5, and lower limbs are 2/5. Electrocardiogram (ECG) revealed wide QRS complex, monomorphic ventricular tachycardia (VT) with ST-segment depression and long QT interval. Serum potassium level was extremely low as 1.0 mEq/L. This led to periodic hypokalemic paralysis. Due to severe hypokalemia with possible atrioventricular block, the patient was admitted to the intensive care unit. During hospitalization, his potassium level returned to 5.1 mEq/L on the first day. He had a low level of thyroid stimulating hormone (TSH) of <0.03 micro-IU/mL (normal range: 0.25-4.00) and a high free thyroxine (T4) level of 2.43 ng/dL (normal range: 0.89-1.79 ng/dL). Therefore, hyperthyroidism was diagnosed, and 5 mg of methimazole was administered twice a day. The patient was discharged on the seventh day after admission. The final diagnosis is thyrotoxic periodic paralysis (TPP), also as known as nocturnal paralysis or night palsy.

Thyrotoxic periodic paralysis complicated by life-threatening acute hypercapnic respiratory failure in a Chinese male with painless thyroiditis.

CONTEXT: Thyrotoxic periodic paralysis (TPP) is a relatively common complication seen in Asian hyperthyroid patients. However, it is a rare occurrence to find a TPP case comprised of acute hypercapnic respiratory failure in patients with painless thyroiditis. PATIENT: A 29-year-old Chinese man presented with flaccid paralysis of all four limbs and he was brought to emergency room. Severe hypokalemia was found on admission. Although treatment had been initiated with potassium chloride supplementation, he went on to develop acute hypercapnic respiratory failure likely due to muscle fatigue. The patient was intubated for mechanical ventilatory support. Once his serum potassium levels were normalized, he was able to be weaned off ventilator support. Thyroid function tests showed elevated free thyroxine concentration and low thyroid-stimulating hormone concentration. He underwent a thyroid uptake scan with 131I which revealed decreased uptake rate of thyroid area. Based on the patient's clinical presentation and associated findings, we diagnosed him with TPP due to painless thyroiditis. We have reviewed TPP cases caused by painless thyroiditis and TPP cases associated with acute hypercapnic respiratory failure. CONCLUSION: It is important to note that potentially fatal complications such as acute hypercapnic respiratory failure might occur in acute attacks of TPP even in cases of TPP due to painless thyroiditis.

Changing Management Guidelines in Thyrotoxic Hypokalemic Periodic Paralysis.

BACKGROUND: Periodic paralysis is a rare complication of hyperthyroidism. Patients of East Asian descent are most commonly affected. Presentation is characterized by recurrent episodes of painless, abrupt-onset weakness, with laboratory evaluation characterized by profound hypokalemia. Underlying hyperthyroidism may not be clinically evident, but differentiation from the familial variant is critical due to differing treatment pathways. CASE REPORT: We describe the presentation of a 22-year-old man with recurrent relapsing-remitting weakness with undiagnosed hyperthyroidism. WHY SHOULD AN EMERGENCY PHYSICIAN BE AWARE OF THIS?: In patients with acute-onset paralysis with significant hypokalemia, or relapsing-remitting symptoms, hyperthyroidism should be suspected. Obese patients are at an especially increased risk due to underlying insulin resistance, which enhances basal sodium-potassium ATPase function. Hypokalemia is functional in nature. Nonselective ß-blockers (such as propranolol) should be considered first line, as they simultaneously decrease ATPase activity, limit insulin secretion, and address the underlying disorder. Administration of > 50 mEq of exogenous potassium places patients at risk of dysrhythmias from rebound hyperkalemia.