Recognizing the underlying causes of hypokalemic paralysis seems to be essential for the appropriate management of affected patients and their prevention of recurrent attacks. There is, however, a paucity of documented reports on the etiology of hypokalemic paralysis in Korea. We retrospectively analyzed 34 patients with acute flaccid weakness due to hypokalaemia who were admitted during the 5-year study period in order to determine the spectrum of hypokalemic paralysis in Korea and to identify the differences in clinical parameters all across the causes of hypokalemic paralysis. We divided those 34 patients into 3 groups; the 1st group, idiopathic hypokalemic periodic paralysis (HPP), the 2nd, thyrotoxic periodic paralysis (TPP), and the 3rd group, secondary hypokalemic paralysis (HP) without TPP. Seven of the patients (20.6%) were diagnosed as idiopathic HPP considered the sporadic form, and 27 patients (79.4%) as secondary HP. Among the patients diagnosed as secondary HP, 16 patients (47.1%) had TPP. Patients of secondary hypokalemic paralysis without TPP required a longer recovery time compared with those who had either idiopathic HPP or TPP. This is due to the fact that patients of secondary HP had a significantly negative total body potassium balance, whereas idiopathic HPP and TPP were only associated with intracellular shift of potassium. Most of the TPP patients included in our study had overt thyrotoxicosis while 3 patients had subclinical thyrotoxicosis. This study shows that TPP is the most common cause of hypokalemic paralysis in Korea. And we suggest that doctors should consider the presence of TPP in patients of hypokalemic paralysis even if they clinically appear to be euthyroid state.
Hypokalemic periodic paralysis; Thyrotoxic periodic paralysis; Hypokalemic paralysis
A comprehensive analysis has not been performed on patients with thyrotoxic periodic paralysis (TPP) characterized by acute hypokalemia and paralysis in the setting of thyrotoxicosis.
The aim of this study was to analyze the detailed symptomatology of thyrotoxicosis and precipitating factors for the attack in a large cohort of TPP patients.
Patients and methods
A prospective observational study enrolled patients with TPP consecutively over 10 years at an academic medical center. Clinical features, including signs/symptoms of thyrotoxicosis and precipitating factors, were analyzed. The Wayne's index was used to assess the severity of thyrotoxicosis at presentation. Patients who agreed to receive an oral glucose-loading test after recovery were evaluated.
Among the 135 TPP patients (male:female, 130:5), 70% of paralytic attacks occurred in the morning, especially during the seasons of summer and fall. Two-thirds of patients did not have a known family or personal history of hyperthyroidism. Only 17% of TPP patients manifested overt signs/symptoms of thyrotoxicosis (Wayne's index >19). A clear precipitating factor, such as high carbohydrate load, acute upper respiratory tract infection, strenuous exercise, high-salt diet, or the use of steroids or bronchodilators, was identified in only 34% of TPP patients. A glucose load to stimulate insulin secretion induced acute hypokalemia (K+2.47±0.6 mmol/l) with reparalysis in only 18% (10/55) of TPP patients.
Most TPP patients have only subtle clinical signs/symptoms of thyrotoxicosis and only a small fraction has clear precipitating factors. In addition to the effects of hyperinsulinemia, other insulin-independent mechanisms may participate in the pathogenesis of TPP.
Thyrotoxic periodic paralysis (TPP) is a rare manifestation of hyperthyroidism characterized by muscle weakness and hypokalemia. All ethnicities can be affected, but TPP typically presents in men of Asian descent. The most common cause of TPP in thyrotoxicosis is Graves' disease. However, TPP can occur with any form of thyrotoxicosis. Up to our knowledge, very few cases ever reported the relationship between TPP and painless thyroiditis. We herein report a 25-yr-old Korean man who suffered from flaccid paralysis of the lower extremities and numbness of hands. The patient was subsequently diagnosed as having TPP associated with transient thyrotoxicosis due to painless thyroiditis. The paralytic attack did not recur after improving the thyroid function. Therefore, it is necessary that early diagnosis of TPP due to transient thyrotoxicosis is made to administer definite treatment and prevent recurrent paralysis.
Thyrotoxic Hypokalemic Periodic Paralysis; Painless Thyroiditis; Thyrotoxicosis
Objective. Thyrotoxic periodic paralysis (TPP), a known condition in Asian men, is becoming increasingly common in men from Western countries. Since suspicion for TPP as a differential in diagnosis is of utmost importance to avoid overcorrection of hypokalemia and other complications, we are reporting a case of TPP in a 25-year-old Caucasian male. Methods. The patient presented with intermittent lower extremity weakness after consumption of a large high-carbohydrate meal. Clinical examination revealed diffusely enlarged thyroid gland, no muscle power in lower extremities, tremors, and brisk deep tendon reflexes. Results. Clinical and laboratory findings were consistent with Graves' disease and the patient had hypokalemia. The patient responded to potassium repletion and was treated with propylthiouracil and propranolol. After treatment with radioactive iodine, the patient developed postablative hypothyroidism for which he was treated with levothyroxine. Conclusion. Since this condition is overlooked by physicians in Western countries, we present a case of TPP in a Caucasian male thus showing the importance of consideration of TPP in Caucasians despite its rare occurrence and the need for prompt diagnosis to avoid the danger of hyperkalemia in management of the paralytic attack in TPP patients.
Thyrotoxic periodic paralysis (TPP), a disorder most commonly seen in Asian men, is characterized by abrupt onset of hypokalemia and paralysis. The condition primarily affects the lower extremities and is secondary to thyrotoxicosis. The underlying hyperthyroidism is often subtle causing difficulty in early diagnosis. Factors like high-carbohydrate meal exercise, steroid, and stress can precipitate an attack of TPP. Evidence is building up showing role of genetic mutations in Kir2.6 channel in the pathogenesis of TPP. Loss of function of Kir2.6 together with increased activity of Na+/K+ ATPase may trigger a positive feed-forward cycle of hypokalemia. Biochemical hyperthyroidism with normal urinary potassium excretion and ECG changes are characteristic of TPP. Treatment with low-dose potassium supplements and nonselective beta-blockers should be initiated upon diagnosis, and the serum potassium level should be frequently monitored to prevent rebound hyperkalemia.
Thyrotoxic hypokalemic periodic paralysis (TPP) is characterized by acute attacks of weakness, hypokalemia, and thyrotoxicosis of various etiologies. These transient attacks resemble those of patients with familial hypokalemic periodic paralysis (hypoKPP) and resolve with treatment of the underlying hyperthyroidism. Because of the phenotypic similarity of these conditions, we hypothesized that TPP might also be a channelopathy. While sequencing candidate genes, we identified a previously unreported gene (not present in human sequence databases) that encodes an inwardly rectifying potassium (Kir) channel, Kir2.6. This channel, nearly identical to Kir2.2, is expressed in skeletal muscle and is transcriptionally regulated by thyroid hormone. Expression of Kir2.6 in mammalian cells revealed normal Kir currents in whole-cell and single-channel recordings. Kir2.6 mutations were present in up to 33% of the unrelated TPP patients in our collection. Some of these mutations clearly alter a variety of Kir2.6 properties, all altering muscle membrane excitability leading to paralysis.
We present a case of fatal rebound hyperkalemia in a patient with thyrotoxic periodic paralysis (TPP) treated with potassium supplementation. Although TPP is a rare hyperthyroidism-related endocrine disorder seen predominantly in men of Asian origin, the diagnosis should be considered in patients of non-Asian origins presenting with hypokalemia, muscle weakness or acute paralysis. The condition may present as a life threatening emergency and unfamiliarity with the disease could result in a fatal outcome. Immediate therapy with potassium chloride supplementation may foster a rapid recovery of muscle strength and prevent cardiac arrhythmias secondary to hypokalemia, but with a risk of rebound hyperkalemia.
Acute hypokalemic paralysis, characterized by acute flaccid paralysis is primarily a calcium channelopathy, but secondary causes like renal tubular acidosis (RTA), thyrotoxic periodic paralysis (TPP), primary hyperaldosteronism, Gitelman’s syndrome are also frequent.
To study the etiology, varied presentations, and outcome after therapy of patients with hypokalemic paralysis.
Materials And Methods:
All patients who presented with acute flaccid paralysis with hypokalemia from October 2009 to September 2011 were included in the study. A detailed physical examination and laboratory tests including serum electrolytes, serum creatine phosphokinase (CPK), urine analysis, arterial blood gas analysis, thyroid hormones estimation, and electrocardiogram were carried out. Patients were further investigated for any secondary causes and treated with potassium supplementation.
The study included 56 patients aged 15-92 years (mean 36.76 ± 13.72), including 15 female patients. Twenty-four patients had hypokalemic paralysis due to secondary cause, which included 4 with distal RTA, 4 with Gitelman syndrome, 3 with TPP, 2 each with hypothyroidism, gastroenteritis, and Liddle’s syndrome, 1 primary hyperaldosteronism, 3 with alcoholism, and 1 with dengue fever. Two female patients were antinuclear antibody-positive. Eleven patient had atypical presentation (neck muscle weakness in 4, bladder involvement in 3, 1 each with finger drop and foot drop, tetany in 1, and calf hypertrophy in 1), and 2 patient had respiratory paralysis. Five patients had positive family history of similar illness. All patients improved dramatically with potassium supplementation.
A high percentage (42.9%) of secondary cause for hypokalemic paralysis warrants that the underlying cause must be adequately addressed to prevent the persistence or recurrence of paralysis.
Hypokalemia; paralysis; secondary causes
Periodic paralysis in the setting of hypokalemia can be the result of several underlying conditions, requiring systematic evaluation. Thyrotoxic periodic paralysis (TPP), a curable cause of hypokalemic periodic paralysis, can often be the first manifestation of thyrotoxicosis. Because the signs and symptoms of thyrotoxicosis can be subtle and clouded by the clinical distress of the patient, the diagnosis of the underlying metabolic disorder can be overlooked. The authors report a case of TPP in a young Chinese man in whom the diagnosis of thyrotoxicosis was initially missed. This case illustrates the lack of awareness of TPP among many physicians, delay in the diagnosis of TPP and the importance of performing thyroid function testing in all cases of periodic paralysis.
Thyrotoxic periodic paralysis (TPP) is a rare complication of hyperthyroidism, with recurrent muscle paralysis and hypokalemia that are caused by an intracellular shift of potassium. TPP is relatively common in Asian males, but is extremely rare in children and adolescents, even for those of Asian descent. We describe a 16-year-old Korean adolescent presenting with a two-week history of episodic leg weakness in the morning. He showed sinus tachycardia, lower leg weakness, and hypokalemia. Thyroid function test showed hyperthyroidism, and thyroid ultrasonography revealed a diffuse enlarged thyroid with increased vascularity, consistent with Graves' disease. He was treated with β-adrenergic blocker and antithyroid drugs. He has been symptom free for one year, as his hyperthyroidism has been controlled well with antithyroid drugs. TPP should be considered in children and adolescents with acute paralysis of the lower extremities and hypokalemia.
Thyrotoxic periodic paralysis; Graves' disease; Adolescent; Korean
Background: periodic paralysis related to hypokalemia is seldom reported in thyrotoxicosis, and it usually occurs in Asian males.
Patients and methods: Two Romanian (Caucasian) young patients presented with hypokalemic paralysis. TSH, FT4, TT3 was measured by immunochemiluminescence.
Case report 1. Patient O.R, aged 19, presented marked asthenia and lower limbs paralysis, following high carbohydrate meal. He declared 10 kg weight loss on hypocaloric diet and mild sweating. Biochemical data revealed moderate hypokalemia (K+=2.6 mmol/L) and thyrotoxicosis (TSH<0.03 mIU/L, FT4=30 pmol/L, TT3=315 ng/dL).
Case report 2. Patient T.A., aged 18, presented 2 episodes of weakness and flaccid paralysis, with hypokalemia, precipitated by effort, without any sign of thyrotoxicosis. Biochemical data revealed severe hypokalemia (K+=1.8 mmol/L) and thyrotoxicosis (TSH<0.03 mIU/L, FT4=24 pmol/L, TT3=190 ng/dL). Treatment with intravenous potassium, thereafter methimazole and propranolol were administered in both cases, with the maintenance of normal kalemia and thyrotoxicosis’ control.
Conclusion: these 2 cases of hypokalemic periodic paralysis occurring in young Caucasian teenagers with mild thyrotoxicosis underlined the importance of thyroid screening in patients with symptomatic hypokalemia, even in the absence of symptoms and signs of thyrotoxicosis.
Abbreviations: THPP=Thyrotoxic periodic paralysis, BMI=body mass index, TRAb=TSH receptor antibody, ECG=electrocardiogram.
hypokalemic paralysis; thyrotoxicosis; teenagers
Objective. Thyrotoxic periodic paralysis (TPP) is a potentially life-threatening complication of Graves' disease (GD). The present study compared the long-term efficacy of antithyroid drugs (ATD), radioactive iodine (RAI), and surgery in GD/TPP. Methods. Sixteen patients with GD/TPP were followed over a 14-year period. ATD was generally prescribed upfront for 12–18 months before RAI or surgery was considered. Outcomes such as thyrotoxic or TPP relapses were compared between the three modalities. Results. Eight (50.0%) patients had ATD alone, 4 (25.0%) had RAI, and 4 (25.0%) had surgery as primary treatment. Despite being able to withdraw ATD in all 8 patients for 37.5 (22–247) months, all subsequently developed thyrotoxic relapses and 4 (50.0%) had ≥1 TPP relapses. Of the four patients who had RAI, two (50%) developed thyrotoxic relapse after 12 and 29 months, respectively, and two (50.0%) became hypothyroid. The median required RAI dose to render hypothyroidism was 550 (350–700) MBq. Of the 4 patients who underwent surgery, none developed relapses but all became hypothyroid. Conclusion. To minimize future relapses, more definitive primary treatment such as RAI or surgery is preferred over ATD alone. If RAI is chosen over surgery, a higher dose (>550 MBq) is recommended.
This article aims at highlighting the importance of suspecting thyrotoxicosis in cases of recurrent periodic flaccid paralysis; especially in Asian men to facilitate early diagnosis of the former condition. A case report of a 28 year old male patient with recurrent periodic flaccid paralysis has been presented. Hypokalemia secondary to thyrotoxicosis was diagnosed as the cause of the paralysis. The patient was given oral potassium intervention over 24 hours. The patient showed complete recovery after the medical intervention and was discharged after 24 hours with no residual paralysis. Thyrotoxic periodic paralysis (TPP) is a complication of thyrotoxicosis, more common amongst males in Asia. It presents as acute flaccid paralysis in a case of hyperthyroidism with associated hypokalemia. The features of thyrotoxicosis may be subtle or absent. Thus, in cases of recurrent or acute flaccid muscle paralysis, it is important to consider thyrotoxicosis as one of the possible causes, and take measures accordingly.
Acute flaccid periodic paralysis; genetic predisposition; hypokalemia; oral potassium; thyrotoxicosis
We present three cases of thyrotoxic periodic paralysis (TPP) due to painless thyroiditis presenting as acute quadriparesis. All responded to potassium supplementation and propranolol. TPP may be due to thyrotoxicosis of any etiology, commonly Grave's disease. The absence of clinical signs of thyrotoxicosis can delay diagnosis and treatment. Thyroid function tests should be a routine evaluation in all cases of hypokalemic periodic paralysis.
Hypokalaemia; periodic paralysis; thyrotoxicosis; thyroiditis
Isolated hepatic perfusion with high-dose chemotherapy is a treatment option for patients with irresectable metastases confined to the liver. Prolonged local control and impact on survival have been claimed. Major drawbacks are magnitude and costs of the procedure. We developed an isolated hypoxic hepatic perfusion (IHHP) with retrograde outflow without the need for a heart-lung machine.
Patients and Methods
Twenty-four consecutive patients with irresectable metastases of various origins were treated. IHHP inflow was via the hepatic artery, outflow via the portal vein with occlusion of the retrohepatic caval vein. Radiolabeled albumine was used for leakage monitoring. Melphalan was used at 1–2 mg/kg. A 25-minute perfusion period was followed by a complete washout. Local and systemic melphalan concentrations were determined.
Compared with oxygenated classical IHP, the IHPP procedure reduced operation time from >8 h to 4 hours, blood loss from >4000 to 900 cc and saved material and personnel costs. Leakage was 0% with negligible systemic toxicity and 0% perioperative mortality. Tumor response: complete response (CR) in 4%, partial response (PR) in 58%, and stable disease (SD) in 13%. Median time to progression was 9 months (2–24 months); pharmacokinetics demonstrated intrahepatic melphalan concentrations more than 9 fold higher than postperfusion systemic concentrations.
IHPP is a relatively simple procedure with reduced costs, reduced blood loss, no mortality, limited toxicity, and response rates comparable to classic IHP. The median duration of 9 months of tumor control should be improved. Hereto, vasoactive drugs, will be explored in further studies.
Isolated hepatic perfusion; Retrograde outflow; Hypoxic; Metastasis; Melphalan
Methods: 22 subjects were studied from two families with HPP caused by R528H mutation, four patients with thyrotoxic periodic paralysis, 15 normal controls, and four controls with hyperthyroidism. All family members were submitted to clinical evaluation, electrophysiological exercise testing, and DNA analysis. Patients with thyrotoxic periodic paralysis had exercise tests before and after treatment of their hyperthyroidism.
Results: Abnormal responses to the exercise tests were obtained only in subjects with recent attacks of weakness. They were not correlated with genotype, as asymptomatic carriers were unaffected. Patients with thyrotoxic periodic paralysis showed pronounced impairment while they were hyperthyroid, but improved when they were euthyroid. One patient with HPP and chronic KCl use had an increase in amplitude potentials over ~20 minutes, possibly related to alteration of potassium homeostasis.
Conclusions: The exercise test is a useful diagnostic test for periodic paralysis, but in the absence of recent weakness negative results must be viewed with caution. It has advantages over the DNA test in being a non-invasive functional test that can provide insights into abnormalities of muscle excitability.
Objectives. To describe 2 cases of thyrotoxic periodic paralysis. Methods. We report of 2 cases of thyrotoxic periodic paralysis in 2 individuals from 2 different backgrounds with emphasis on their presentation and treatment. We also conducted a literature search to put together an update review of thyrotoxic periodic paralysis. Results. A 47-year-old Chinese and 28-year-old Caucasian male presented with profound yet reversible weakness associated with hypokalemia on admission bloods and thyrotoxicosis. Both were given definitive therapy to prevent recurrence of attacks with any future relapse of thyrotoxicosis. Conclusion. Thyrotoxic periodic paralysis (TPP) is a rare but potentially serious complication of thyrotoxicosis resulting in temporary but severe muscle weakness. Recent discovery of a novel mutation in the KCNJ18 gene which codes for an inwardly rectifying potassium channel and is controlled by thyroid hormones may provide greater insight into the pathogenesis of TPP.
Hyperthyroidism may be associated with hypokalemic periodic paralysis. Two cases are presented demonstrating intermittent attacks of flaccid paralysis associated with clinical symptoms, signs and laboratory findings of hyperthyroidism. During an attack, one patient had a serum potassium of 2.1 mEq. per litre.
Various factors such as trauma, exposure to cold, excessive carbohydrate ingestion and certain medications have been stated to precipitate an episode of paralysis. Attacks may range from mild weakness to generalized flaccid paralysis with loss of deep tendon reflexes. Several reported patients have died owing to cardiac arrest or respiratory paralysis.
During attacks, the serum potassium is usually in the range of 2.2 to 3.2 mEq. per litre. It is postulated that a metabolic abnormality affecting the muscle-cell membrane can occur in the hyperthyroid state resulting in a shift of potassium to the intracellular position, thus producing a situation of hyperpolarization of the muscle-cell membrane which in turn alters the muscle contractibility.
The importance of recognizing the unusual association of hypokalemic periodic paralysis with hyperthyroidism is stressed because, with successful treatment of the hyperthyroidism, the episodes of paralysis disappear.
Neck ventroflexion in cats has different causes; however, the most common is the hypokalemia associated with flaccid paralysis secondary to chronic renal failure. In humans, the most common causes of acute flaccid paralysis are hypokalemia precipitated by thyrotoxicosis and familial forms linked to mutations in sodium, potassium, and calcium channel genes. Here, we describe the sequencing and analysis of skeletal muscle ion channels in Felis catus that could be related to periodic paralyses in humans, contributing to the understanding of the genetic susceptibility to feline neck ventroflexion and paralysis. We studied genomic DNA from eleven cats, including five animals that were hyperthyroid with hypokalemia, although only one presented with muscle weakness, and six healthy control domestic cats. We identified the ion channel ortholog genes KCNJ2, KCNJ12, KCNJ14, CACNA1S and SCN4A in the Felis catus genome, together with several polymorphic variants. Upon comparative alignment with other genomes, we found that Felis catus provides evidence for a high genomic conservation of ion channel sequences. Although we hypothesized that neck ventroflexion in cats could be associated with a thyrotoxic or familial periodic paralysis channel mutation, we did not identify any previously detected human channel mutation in the hyperthyroid cat presenting hypokalemia. However, based on the small number of affected cats in this study, we cannot yet rule out this molecular mechanism. Notwithstanding, hyperthyroidism should still be considered as a differential diagnosis in hypokalemic feline paralysis.
Potassium channel; Inward rectifier; Felis catus; Kir2.x; KCNJ2; KCNJ12; KCNJ18; CACNA1S; SCN4A; Cat
Thyrotoxic Periodic Paralysis (TPP) is a rare and life threatening condition commonly occurring in young Asian males. It is characterized by acute paralytic attacks and hypokalemia in association with thyrotoxicosis. Serum potassium levels may be normal in rare cases of TPP. The diagnosis of normokalemic TPP may be overlooked and/or delayed in most cases. Here, we describe a 32-year-old Iranian man with normokalemic TPP misdiagnosed as somatization disorder with the correct diagnosis made one year after the onset of symptoms.
hypokalemia; hypokalemic periodic paralysis; thyrotoxic periodic paralysis; normokalemic; periodic paralysis
Thyrotoxic periodic paralysis (TPP) attacks are characterized as recurrent, transient episodes of muscle weakness that range from mild weakness to complete flaccid paralysis. Episodes of weakness are accompanied by hypokalemia, which left untreated can lead to life-threatening arrhythmias (6). In this case study, we followed a patient’s potassium levels analyzing how they correlate with electrocardiogram changes seen while treating his hypokalemia and ultimately his paralysis.
The aim of the present study was to investigate the effect of erythropoietin (EPO) loading chitosan-tripolyphosphate (CS-TPP) nanoparticles on an immunoglobulin A nephropathy (IgAN) rat model. CS-TPP nanoparticles were produced from CS and TPP and EPO was loaded by mixing with the nanoparticles. The IgAN rat models were randomly divided into three groups: the CS-TPP-EPO group, CS-TPP group and EPO group. Hemoglobin (Hb), blood urea nitrogen (BUN) and creatinine (Cr) levels were measured in each group using a Biochemical Analyzer (Hitachi, Tokyo, Japan). The average size of nanoparticles was 485±12 nm and the encapsulation efficiency of EPO was 78.45%. The EPO release curve in CS-TPP-EPO nanoparticles exhibited a biphasic distribution in vitro. The levels of BUN and Cr in the CS-TPP-EPO group were significantly lower compared with the control group (P<0.05); however, the level of Hb in the CS-TPP-EPO group was higher compared with the other groups (P<0.05). The changes in Hb, BUN and Cr in the CS-TPP-EPO group were maintained for less than one week following the end of the treatment with CS-TPP-EPO nanoparticles. In conclusion, the CS-TPP-EPO nanoparticles had a lower toxicity compared with EPO and CS-TPP treatment. Furthermore, CS-TPP-EPO may improve the therapeutic effect in the IgAN model. This suggests that CS-TPP-EPO nanoparticles may be a potential therapeutic drug for the treatment of patients with IgAN.
IgA nephropathy; renal function; erythropoietin; nanoparticles; chitosan-tripolyphosphate
A 16-year-old Japanese boy with a history of truancy had been treated at a psychiatric clinic. When the patient was referred to us for hypokalemia-associated paralysis, the diagnosis of thyrotoxic hypokalemic periodic paralysis was made, common in Asian men. Subsequently, the patient was found to have persistently high plasma renin and aldos-terone levels. Thus, solute carrier family 12 member 3 gene (SLC12A3) analysis was performed. A novel missense homozygous mutation CTC->CAC at codon 858 (L858H) was found for which the patient was homozygous and his non-consanguineous parents heterozygote. These findings indicated that the patient developed hypokalemia-associated paralysis concurrently with thyrotoxicosis and Gitelman's syndrome. This case underscores the importance of careful examinations of adolescents with complaints of truancy as well as of precise determinations of the causes of hypokalemia-associated paralysis.
hypokalemic periodic paralysis; thyrotoxicosis; Gitelman's syndrome; adolescents; truancy.
Hypokalemic paralysis is characterized by episodes of acute muscle weakness associated with hypokalemia. In this study, we evaluated the possible etiological factors in patients of hypokalemic paralysis.
Materials and Methods:
We reviewed the records of 29 patients who were admitted with a diagnosis of hypokalemic paralysis. Modified Guillain-Barre´ Syndrome disability scale was used to grade the disability.
In this study, 15 (51.7%) patients had secondary causes of hypokalemic paralysis and 14 patients (42.3%) had idiopathic hypokalemic paralysis. Thyrotoxicosis was present in six patients (20.6%), dengue infection in four patients (13.7%), distal renal tubular acidosis in three patients (10.3%), Gitelman syndrome in one patient (3.4%), and Conn's syndrome in one patient (3.4%). Preceding history of fever and rapid recovery was seen in dengue infection-induced hypokalemic paralysis. Approximately 62% patients had elevated serum creatinine phosphokinase. All patients had recovered completely following potassium supplementation. Patients with secondary causes were older in age, had significantly more disability, lower serum potassium levels, and took longer time to recover.
In conclusion, more than half of patients had secondary causes responsible for hypokalemic paralysis. Dengue virus infection was the second leading cause of hypokalemic paralysis, after thyrotoxicosis. Presence of severe disability, severe hypokalemia, and a late disease onset suggested secondary hypokalemic paralysis.
Acute flaccid paralysis; dengue virus; hypokalemia; hypokalemic paralysis
Mammalian cells obtain vitamin B1 (thiamin) from their surrounding environment and convert it to thiamin pyrophosphate (TPP) in the cytoplasm. Most of TPP is then transported into the mitochondria via a carrier-mediated process that involves the mitochondrial thiamin pyrophosphate transporter (MTPPT). Knowledge about the physiological parameters of the MTPP-mediated uptake process, MTPPT targeting and the impact of clinical mutations in MTPPT in patients with Amish lethal microcephaly and neuropathy and bilateral striatal necrosis are not fully elucidated, and thus, were addressed in this study using custom-made 3H-TPP as a substrate and mitochondria isolated from mouse liver and human-derived liver HepG2 cells. Results showed 3H-TPP uptake by mouse liver mitochondria to be pH-independent, saturable (Km = 6.79±0.53 µM), and specific for TPP. MTPPT protein was expressed in mouse liver and HepG2 cells, and confocal images showed a human (h)MTPPT-GFP construct to be targeted to mitochondria of HepG2 cells. A serial truncation analysis revealed that all three modules of hMTPPT protein cooperated (although at different levels of efficiency) in mitochondrial targeting rather than acting autonomously as independent targeting module. Finally, the hMTPPT clinical mutants (G125S and G177A) showed proper mitochondrial targeting but displayed significant inhibition in 3H-TPP uptake and a decrease in level of expression of the MTPPT protein. These findings advance our knowledge of the physiology and cell biology of the mitochondrial TPP uptake process. The results also show that clinical mutations in the hMTPPT system impair its functionality via affecting its level of expression with no effect on its targeting to mitochondria.