1/108. C-terminal HERG mutations: the role of hypokalemia and a KCNQ1-associated mutation in cardiac event occurrence.BACKGROUND: The long-QT syndrome (LQTS) is a genetically heterogeneous disease in which 4 genes encoding ion-channel subunits have been identified. Most of the mutations have been determined in the transmembrane domains of the cardiac potassium channel genes KCNQ1 and HERG. In this study, we investigated the 3' part of HERG for mutations. methods AND RESULTS: New specific primers allowed the amplification of the 3' part of HERG, the identification of 2 missense mutations, S818L and V822 M, in the putative cyclic nucleotide binding domain, and a 1-bp insertion, 3108 1G. hypokalemia was a triggering factor for torsade de pointes in 2 of the probands of these families. Lastly, in a large family, a maternally inherited G to A transition was found in the splicing donor consensus site of HERG, 2592 1G-A, and a paternally inherited mutation, A341E, was identified in KCNQ1. The 2 more severely affected sisters bore both mutations. CONCLUSIONS: The discovery of mutations in the C-terminal part of HERG emphasizes that this region plays a significant role in cardiac repolarization. Clinical data suggests that these mutations may be less malignant than mutations occurring in the pore region, but they can become clinically significant in cases of hypokalemia. The first description of 2 patients with double heterozygosity associated with a dramatic malignant phenotype implies that genetic analysis of severely affected young patients should include an investigation for >1 mutation in the LQT genes.- - - - - - - - - - ranking = 1keywords = long (Clic here for more details about this article) |
2/108. torsades de pointes ventricular tachycardia induced by clarithromycin and disopyramide in the presence of hypokalemia.We report a 76-year-old woman who developed TdP ventricular tachycardia induced by combined use of clarithromycin and disopyramide. She had a history of myocardial infarction 5 years earlier and has taken disopyramide for supraventricular arrhythmias. In addition, she had taken clarithromycin for upper respiratory tract infection. On admission, an ECG showed prolongation of QTc interval to 0.71 seconds and self-terminating TdP occurred several times. disopyramide was metabolized by the cytochrome enzyme CYP3A4 and clarithromycin competitively inhibits this enzyme, probably resulting in an increase in plasma concentration of disopyramide. We should consider this possibility when prescribing clarithromycin in combination with antiarrhythmic agent disopyramide.- - - - - - - - - - ranking = 1keywords = long (Clic here for more details about this article) |
3/108. hypokalemia with syncope caused by habitual drinking of oolong tea.A 61-year-old woman developed hypokalemia, atrioventricular block and ventricular tachycardia with syncope after habitual drinking 2 to 3 liters of oolong tea per day. She had been suffering from rheumatoid arthritis and sjogren's syndrome and her serum albumin was decreased (2.9 g/dl). Oolong tea contains caffeine at approximately 20 mg/dl. Great quantities of caffeine can induce hypokalemia. The serum protein binding caffeine is albumin. Accordingly, in patients with hypoalbuminemia, caffeine is apt to induce hypokalemia. This case suggested that great quantities of oolong tea, one of the so-called "healthy" drinks, result in serious symptoms for patients with hypoalbuminemia.- - - - - - - - - - ranking = 7keywords = long (Clic here for more details about this article) |
4/108. Licorice-induced hypokalemic myopathy and hypokalemic renal tubular damage in anorexia nervosa.A patient with a history of anorexia nervosa developed licorice-induced hypokalemic myopathy. With potassium replacement, high CPK blood level and myopathic signs returned to normal. However, the patient manifested persistent hypokalemia and impaired renal function to concentrate and acidify the urine. Renal biopsy demonstrated intense degeneration and vacuolation of tubules with a normal glomerus which was consistent with hypokalemic nephropathy. Prolonged hypokalemia in anorexia nervosa is sometimes attributed to surreptitious purging or taking diuretics, but it is necessary to check the urine pH, the urine-specific gravity, and the urine potassium level in order to find underlying renal damage even after hypokalemic myopathy is treated successfully.- - - - - - - - - - ranking = 1keywords = long (Clic here for more details about this article) |
5/108. Prominent bifid T waves observed in the QT prolongation caused by complete atrioventricular blockade in a hypokalemic diabetic patient.A 63-year-old diabetic man was admitted with general fatigue. Electrocardiogram (ECG) on admission showed complete atrioventricular (AV) blockade associated with prominent bifid T waves. The second component of the bifid T waves was distinguished from U waves by the beat-to-beat varying bifidity and the nadir between the two components located at > or = 1 mm above the isoelectric line. Range of absolute QT interval was 535 to 650 ms. hypokalemia (3.6 mEq/L) was noted at admission. Partial restoration of the potassium level (3.9 mEq/L) prior to temporary ventricular demand pacing obscured the bifid T waves and attenuated the QT prolongation and dispersion to some extent (absolute QT interval ranging 520 to 620 ms). It was concluded that marked bradycardia caused by complete AV blockade (ie, a junctional escaped rhythm at a rate of 42 beats/min), hypokalemia, and underlying diabetes mellitus contributed in concert to the QT prolongation and dispersion leading to the prominent bifid T waves.- - - - - - - - - - ranking = 6keywords = long (Clic here for more details about this article) |
6/108. Torsade de pointes associated with hypokalemia after anthracycline treatment in a patient with acute lymphocytic leukemia.Severe dose-dependent anthracycline cardiotoxicity is reported to cause myocardial damage resulting in congestive heart failure. However, torsade de pointes, a life-threatening arrhythmia caused by chronic anthracycline cardiotoxicity, has not been reported previously. A 16-year-old girl who developed torsade de pointes after 6 months of chemotherapy for acute lymphocytic leukemia (French-American-British classification L2) is described. When the patient was readmitted to the hospital because of syncope, peripheral blood and bone marrow analysis indicated a relapse. In addition, the patient was hypokalemic. Twenty-four-hour ambulatory electrocardiographic monitoring demonstrated QT prolongation and an episode of torsade de pointes. The electrocardiographic changes and arrhythmia improved after correction of the hypokalemia. An inverse correlation between leukocyte count and hypokalemia was observed. The patient died from pulmonary hemorrhage. autopsy examination demonstrated myocardial degeneration consistent with damage induced by antineoplastic antibiotics. The cumulative dose of anthracycline and anthraquinone was less than the conventional dose limit associated with chronic cardiotoxicity, even for children who are more sensitive to anthracyclines. Torsade de pointes can occur in the setting of chronic anthracycline cardiotoxicity. Therefore, children or young adults who are more sensitive to anthracycline need careful observation that includes electrolyte monitoring, especially for potassium.- - - - - - - - - - ranking = 1keywords = long (Clic here for more details about this article) |
7/108. Low doses of liquorice can induce hypertension encephalopathy.Prolonged ingestion of liquorice is a well-known cause of hypertension due to hypermineralocorticoidism. We describe 2 cases of hypertension encephalopathy (in addition to the classical symptoms of hypertension, hypokalemia and suppression of the renin-aldosterone system) which resulted in pseudohyperaldosteronism syndrome due to the regular daily intake of low doses of liquorice. Glycyrrhizic acid, a component of liquorice, produces both hypermineralocorticism and the onset of encephalopathy through the inhibition of 11beta-hydroxysteroid dehydrogenase. hypertension encephalopathy due to the daily intake of low doses of liquorice, however, has not been previously documented. It is proposed that some people could be susceptible to low doses of glycyrrhizic acid because of a 11beta-hydroxysteroid dehydrogenase deficiency.- - - - - - - - - - ranking = 1keywords = long (Clic here for more details about this article) |
8/108. Hypokalemic rhabdomyolysis and acute renal failure. Occurrence following total parenteral nutrition.A patient experienced severe hypokalemia in the setting of prolonged nasogastric suction and total parenteral nutrition. Severe rhabdomyolysis and acute renal failure ensued. review of the literature failed to disclose a similar case of hypokalemic rhabdomyolysis and acute renal failure, although the syndrome has been associated with other causes of hypokalemia, and its pathophysiology has been investigated in experimental models. The morbidity associated with extensive myonecrosis and severe, acute renal failure in this patient indicates that hypokalemia and other electrolyte abnormalities should be aggressively corrected in similar clinical settings.- - - - - - - - - - ranking = 1keywords = long (Clic here for more details about this article) |
9/108. hypokalemia-induced long qt syndrome with an underlying novel missense mutation in S4-S5 linker of KCNQ1.Congenital long qt syndrome (LQTS) is caused by mutations in at least five genes coding for cardiac potassium or sodium channels that regulate the duration of ventricular action potentials. Acquired LQTS often is associated with drugs or metabolic abnormalities. A 47-year-old woman who presented with marked QT prolongation (QTc = 620 msec(1/2)) and repeated episodes of torsades de pointes associated with hypokalemia (2.6 mEq/L) was screened for mutations in LQTS genes using polymerase chain reaction/single-strand conformation polymorphism (PCR/SSCP). We identified a novel missense mutation in the intracellular linker of S4-S5 domains of KCNQ1, resulting in an amino acid substitution of cysteine for arginine at position 259 (R259C). Whole cell, patch clamp experiments were conducted on COS7 cells transfected with wild-type and/or R259C KCNQ1 with or without KCNE1. Functional analyses of the mutant KCNQ1 subunit on COS7 cells revealed its functional channels in the homozygous state, producing a significantly smaller current than the KCNQ1 channels and a less severe dominant-negative effect on I(Ks). The novel KCNQ1 mutation R259C is the molecular basis for I(Ks) dysfunction underlying an apparently sporadic case of hypokalemia-induced LQTS, consistent with a mild mutation likely to disclose the clinical manifestation of LQTS in a context of severe hypokalemia. Our findings suggest that gene carriers with such mild mutations might not be so rare as commonly expected in patients with acquired LQTS, and stress the importance of mutational analysis for detecting either "silent" forms of congenital LQTS or de novo mutations.- - - - - - - - - - ranking = 6keywords = long (Clic here for more details about this article) |
10/108. Upper limb ischemia induced by chronic licorice ingestion.A young woman had an acute embolic episode that affected her right upper limb. An axillo-brachial thromboembolectomy was performed after which distal pulses were recovered. The patient had a long lasting history, longer than ten years, of continuous licorice ingestion. blood samples showed severe hypokalemia that caused EKG changes. Transesophageal echocardiogram discovered mild mitral valve prolapse. The combination of surgery and potassium supplements was successful in treating this rare and potentially life-threatening disease.- - - - - - - - - - ranking = 2keywords = long (Clic here for more details about this article) |
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