Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0036572 (seizures)
 80,221 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Gain-of-function mutations of the calcium-sensing receptor (CaR) gene cause autosomal dominant and/or sporadic hypocalcemia with hypercalciuria. Because treatment of the hypocalcemia with vitamin D and/or calcium in patients with such mutations results in increased hypercalciuria, nephrocalcinosis, and renal impairment, its use should be limited to alleviating the symptoms of symptomatic patients. Because thiazide diuretics have been successfully used to treat patients with hypercalciuria and hypoparathyroidism, they are theoretically useful in reducing urine calcium excretion and maintaining serum calcium levels in patients with gain-of-function mutations of the CaR gene. In this study, we report on the clinical course, molecular analysis, and effects of hydrochlorothiazide therapy in two Japanese patients with gain-of-function mutations of the CaR gene. Within a few weeks after birth, they developed generalized tonic seizures due to hypocalcemia (serum calcium values: 1.1 mmol/liter and 1.3 mmol/liter, respectively). Despite treatment with the standard dose of 1,25-dihydroxyvitamin D(3) in one patient and 1alpha-hydroxyvitamin D(3) in the other, acceptable serum calcium levels near the lower limit of normal were not established, and their urinary calcium excretion inappropriately increased. Addition of hydrochlorothiazide (1 mg/kg) reduced their urinary calcium excretion and maintained their serum calcium concentrations near the lower limit of normal, allowing the 1,25-dihydroxyvitamin D(3) and 1alpha-hydroxyvitamin D(3) doses to be reduced, and it alleviated their symptoms. A heterozygous missense mutation was identified in both patients. In one patient, the mutation was A843E in the seventh transmembrane domain of the CaR, and in the other it was L125P in the N-terminal extracellular domain. In vitro transient transfection of their mutant CaR cDNAs into HEK293 cells shifted the concentration-response curve of Ca(2+) to the left. In conclusion, two sporadic cases of hypercalciuric hypocalcemia were due to de novo gain-of-function mutations of the CaR gene. Hydrochlorothiazide with vitamin D(3) successfully reduced the patients' urinary calcium excretion and controlled their serum calcium concentrations and symptoms. Thiazide diuretics are effective in patients with gain-of function mutations of the CaR gene.
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PMID:Hydrochlorothiazide effectively reduces urinary calcium excretion in two Japanese patients with gain-of-function mutations of the calcium-sensing receptor gene. 1210 2

A 5-year-old boy had periodic spasms and startle-induced drop attacks. Zonisamide (ZNS) was partially effective for the former seizures, and propranolol for the latter. An add-on therapy with ACTH resulted in a transient disappearance of seizures and an improvement of EEG. However, the patient developed urolithiasis with resultant hematuria and pyelectasis during ACTH therapy. ZNS can induce urolithiasis by increasing urinary pH and calcium (Ca) excretion, and ACTH may facilitate this rare adverse effect of ZNS by further increasing the urinary Ca. Hydrochlorothiazide could resolve the urolithiasis by decreasing the urinary Ca excretion.
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PMID:[Urolithiasis induced by combined ACTH and zonisamide treatment in a patient with startle induced epilepsy]. 1223 54

Hydrochlorothiazide became one of the most commonly prescribed first-line antihypertensive medication, though its use is often complicated with serious side-effects. A 66-year-old female patient with a history of hypertension had suffered a transient loss of consciousness, and referred to our cardiology unit with an ST-segment elevation and giant negative T-waves in V1-2 ECG leads, long QT-segment and elevated serum creatine-kinase (5392 U/L) and troponin I (4,357 ng/ml) levels. Acute myocardial infarction was not proven (later coronarography revealed preserved coronary circulation), but severe hyponatraemia and hypokalaemia was detected, explaining a possible symptomatic seizure, and which could be accounted for a 25 mg daily hydrochlorothiazide antihypertensive treatment and - as a precipitating insult - a one-week history of gastroenteritis. The case-report presents a unique differential diagnostic question where thiazide-induced hyponatraemia and hypokalaemia resulted in a clinical picture sharing some similarities with acute myocardial infarction. This case underlines the serious side-effects of an inappropriately used common antihypertensive medication. Orv. Hetil., 2017, 158(11), 426-431.
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PMID:[Differential diagnostic dilemmas after use of an out-of-date antihypertensive medication. Case report]. 2828 95