Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0020438 (hypercalciuria)
 2,502 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Some children with Bartter syndrome have hypercalciuria. To determine the mechanism for this phenomenon, we studied tubular function and calcium metabolism in six such children. All patients had hypokalemic alkalosis, normotension, hyperreninemia, growth retardation, low fractional distal chloride reabsorption (4/5), and elevated urinary prostaglandin E2 excretion (5/6). In addition, all had hypercalciuria (urinary calcium 6.5 to 25.0 mg/kg/day), with evidence of nephrocalcinosis in five. None, however, had evidence of rickets or hyperparathyroidism. There was a marked elevation in the serum concentration of 1,25-dihydroxyvitamin D in all, and four patients had a response to oral calcium loading suggestive of absorptive hypercalciuria. Five children have had long-term therapy with indomethacin. They have had improvement in hypokalemia and reduced urinary prostaglandin E2 excretion as well as reductions in the serum concentration of 1,25-dihydroxyvitamin D and in urinary calcium excretion. These data suggest that hypercalciuria in some children with Bartter syndrome is associated with an excess of 1,25-dihydroxyvitamin D. The improvement in hypercalciuria with prostaglandin synthesis inhibition may result in part from correction of this vitamin D abnormality.
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PMID:Hypercalciuria with Bartter syndrome: evidence for an abnormality of vitamin D metabolism. 267 27

Hyperprostaglandin E-syndrome (HPS), a recently described variant of Bartter's syndrome (BS), resembles BS in a number of symptoms but is distinct from BS in others. Similar to BS, HPS is characterized by congenital hypokalemic alkalosis, hypertrophy of the juxtaglomerular apparatus, hyperreninemia, secondary hyperaldosteronism, normal blood pressure and renal diabetes insipidus. Other than BS, HPS is constantly associated with chronic hypercalciuria and nephrocalcinosis as well as both renal and systemic PGE2 overproduction. Correction of most of the symptoms in HPS is achieved by permanent inhibition of prostaglandin synthesis with indomethacin. Among the causes leading to HPS, a selective damage of the distal tubule in HPS has been suggested. Therefore, synthesis of Tamm-Horsfall protein (THP), a glycoprotein exclusively produced in the thick ascending limb of the loop of Henle, was measured by ELISA in the urine of seven infant HPS patients (aged 3 to 8 years). Patients were investigated both under constant indomethacin treatment and after a one week period without indomethacin. Nine healthy children (aged 5 months to 10 years) served as controls. In controls mean daily THP excretion was 54.2 +/- 13.9 (median 46.0) mg/24 hr/1.73 m2 whereas in HPS, THP levels were strongly diminished. During withdrawal of indomethacin treatment, mean THP level was 12.7 +/- 10.1 (median 7.2) mg/24 hr/1.73 m2 and 10.3 +/- 10.1 (median 3.5) mg/24 hr/1.73 m2 under indomethacin treatment, respectively. THP excretion values both without indomethacin and under indomethacin treatment were significantly different from controls (P < or = 0.005); however, there was no significant difference between the THP levels during or after cessation of indomethacin treatment. Creatinine clearance in HPS patients was 75.1 +/- 15.9 (median 76.2) ml/min/1.73 m2 without indomethacin and 81.9 +/- 15.1 (median 83.0) ml/min/1.73 m2 under indomethacin treatment. Control values were not obtained. Comparative measurements of THP excretion in six classical BS-patients (aged 3 months to 17 years) revealed normal THP values in two individuals and intermediate levels in the others: the mean level of six BS patients was 30.8 +/- 13.5 (median 25.0) mg/24 hr/1.73 m2 and was thus significantly higher than in HPS both with and without indomethacin treatment (P < or = 0.05). Immunohistochemistry in renal biopsies of three of the HPS patients showed a strong reduction of cortical tubular THP immunoreactivity in two cases and a less pronounced reduction in the third. In situ hybridization using a THP-riboprobe in these three biopsies revealed significantly reduced or absent THP-mRNA levels.(ABSTRACT TRUNCATED AT 400 WORDS)
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PMID:Marked reduction of Tamm-Horsfall protein synthesis in hyperprostaglandin E-syndrome. 837 83

Hypokalemic alkalosis with low blood pressure can be caused by a number of medications or alternatively as an autosomal recessive genetic trait. Molecular genetic approaches to this problem have recently demonstrated that mutations in genes encoding the thiazide-sensitive Na-Cl cotransporter or the bumetanide-sensitive Na-K-2Cl cotransporter produce two distinctive clinical and physiological pictures featuring hypokalemic alkalosis. Mutations in the latter cause a phenotypic picture called Bartter's syndrome that includes marked hypercalciuria and neonatal presentation with marked intravascular volume depletion. Mutations in the former cotransporter result in Gitelman's syndrome, which includes hypocalciuria, hypomagnesemia, and typically older clinical presentation with predominant muscular signs and symptoms. These findings establish the molecular basis of these disorders and indicate that the diverse abnormalities seen in affected patients derive from primary defects in these mediators of cotransport function. Moreover, these findings have implications for normal mechanisms of renal electrolyte homeostasis and for potential phenotypic effects in the more common heterozygous carriers of these mutations.
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PMID:The molecular basis of inherited hypokalemic alkalosis: Bartter's and Gitelman's syndromes. 894 89

Bartter syndrome involves an overlapping set of closely related renal tubular disorders which can be subdivided into at least three clinical phenotypes: (1) classic Bartter syndrome (2) Gitelman syndrome, and (3) a neonatal variant of Bartter syndrome. In contrast to classic Bartter syndrome and Gitelman syndrome, the neonatal variant of Bartter syndrome has both the features of renal tubular hypokalemic alkalosis as well as profound systemic manifestations. Specifically, neonatal Bartter syndrome is characterized by intrauterine polyhydramnios, premature delivery, and life-threatening episodes of fever and dehydration. Most of these infants also have severe hypercalciuria with associated nephrocalcinosis and osteopenia. Over a 22-year period, 20 Costa Rican patients with a congenital syndrome that resembles neonatal Bartter syndrome have been identified and characterized. While these patients exhibit some of the clinical characteristics previously described for neonatal Bartter syndrome, this cohort also has a set of distinct features. They are predominantly female, have a later age of diagnosis, manifest a relatively unique set of physical traits, and appear to have milder clinical disease. Given these differences, it will be important to apply the emerging molecular tools to determine whether the phenotypic variability indicates genetic heterogeneity in neonatal-onset Bartter syndrome.
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PMID:Bartter syndrome in Costa Rica: a description of 20 cases. 920 76

The antenatal variant of Bartter's syndrome is an autosomal recessive kidney disease characterized by polyhydramnios, premature delivery, hypokalemic alkalosis and hypercalciuria. It is genetically heterogeneous, having been linked recently to mutations in an ATP-sensitive, renal outer medullary K+channel, ROMK, and earlier to mutations in the Na-K-2Cl co-transporter, NKCC2. We characterized four of the mutations reported in three heterozygous ROMK variants of antenatal Bartter's and found that each expressed a distinct phenotype in Sf9 cells. One mutation expressed normal function and appears to be an allelic polymorphism. The other three mutations produced channels with significantly reduced K+fluxes. However, the mechanisms in each case were different and reflected abnormalities in phosphorylation, proteolytic processing or protein trafficking. The different mechanisms may be important in the design of appropriate therapy for patients with this disease.
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PMID:Functional consequences of ROMK mutants linked to antenatal Bartter's syndrome and implications for treatment. 958 Jun 61

Antenatal Bartter syndrome is a variant of inherited renal-tubular disorders associated with hypokalemic alkalosis. This disorder typically presents as a life-threatening condition beginning in utero, with marked fetal polyuria that leads to polyhydramnios and premature delivery. Another hallmark of this variant is a marked hypercalciuria and, as a secondary consequence, the development of nephrocalcinosis and osteopenia. We have analyzed 15 probands belonging to 13 families and have performed SSCP analysis of the coding sequence and the exon-intron boundaries of the NKCC2 gene; and we report 14 novel mutations in patients with antenatal Bartter syndrome, as well as the identification of three isoforms of human NKCC2 that arise from alternative splicing.
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PMID:Novel molecular variants of the Na-K-2Cl cotransporter gene are responsible for antenatal Bartter syndrome. 958

This baby boy was born after a pregnancy complicated by severe polyhydramnios at a gestational age of 28 weeks. Analysis of the amniotic fluid had shown a high chloride content, but normal concentrations of sodium, potassium, and calcium. After birth he displayed extreme polyuria, severe renal sodium and chloride loss, and marked hypercalciuria. Five weeks after birth, his sodium chloride loss turned into renal potassium loss, along with a marked decrease in urine output. All these features are characteristic of the neonatal variant of Bartter syndrome. He was discharged after 11 weeks with oral supplements of sodium chloride, potassium gluconate, and 500 ml of fluid. The follow-up for a period of 6 years showed a surprising evolution: he has no hypokalemic alkalosis, no polyuria, and no hypercalciuria; growth and development are within the normal ranges and, at the time of writing, he is a healthy boy needing no medication and with no medical problems whatsoever.
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PMID:Neonatal Bartter syndrome: spontaneous resolution of all signs and symptoms. 963 34

Mutations in genes encoding ion channels have increasingly been identified to cause disease conditions collectively termed channelopathies. Recognizing the molecular basis of an ion channel disease has provided new opportunities for screening, early diagnosis, and therapy of such conditions. This synopsis provides an overview of progress in the identification of molecular defects in inwardly rectifying potassium (Kir) channels. Structurally and functionally distinct from other channel families, Kir channels are ubiquitously expressed and serve functions as diverse as regulation of resting membrane potential, maintenance of K(+) homeostasis, control of heart rate, and hormone secretion. In humans, persistent hyperinsulinemic hypoglycemia of infancy, a disorder affecting the function of pancreatic beta cells, and Bartter's syndrome, characterized by hypokalemic alkalosis, hypercalciuria, increased serum aldosterone, and plasma renin activity, are the two major diseases linked so far to mutations in a Kir channel or associated protein. In addition, the weaver phenotype, a neurological disorder in mice, has also been associated with mutations in a Kir channel subtype. Further genetic linkage analysis and full understanding of the consequence that a defect in a Kir channel would have on disease pathogenesis are among the priorities in this emerging field of molecular medicine.
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PMID:Channelopathies of inwardly rectifying potassium channels. 1054 73

We report clinical data of a female patient with Bartter's syndrome who was initially diagnosed with idiophatic hypercalciuria and, subsequently, with hyperprostaglandin E, syndrome. The patient was born after premature delivery with a history of polyhydramnios. During the first two years of life, in spite of evidence for significant failure to thrive, polyuria and special tendency to dehydration, she had no hypokalemia. The acid-base balance was normal except metabolic acidosis during the first few days after she was born. When hypercalciuria was observed, she was treated with thiazides and a low-salt diet. With such treatment she frequently showed hypokalemic alkalosis. Afterwards, once it was possible to determine the levels of renin and aldosterone and the urinary excretion of PGE2, we suspected the diagnosis. DNA sequencing analysis showed that the patient carried a homozygotic mutation in the KCNJ1 gene, coding for the potassium channel ROMK, which results in the premature termination of the protein. It is the first time that this mutation has been found in Spain. The detection of this mutation confirmed a disease that was initially of uncertain diagnosis.
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PMID:[Neonatal Bartter disease diagnosed with the detection of a mutation of the KCNJ1 gene which codifies the synthesis of the renal ROMK1 potassium channel]. 1179 13

Hypokalemic periodic paralysis can occur secondarily to excessive potassium loss. Thyrotoxicosis, diuretic ingestions, hyperaldosteronism, barium poisoning, Gitelman syndrome, and Bartter syndrome are among the disorders causing secondary hypokalemic periodic paralysis. Clinical presentation of Bartter syndrome with hypokalemic periodic paralysis is rare. A 12-year-old boy was admitted to our hospital because of transient paralysis. He had been suffering from transient weakness attacks for 2 years and had had a total of 10 attacks, lasting 1 to 3 days. He had growth retardation, polyuria, and polydipsia. Laboratory examinations revealed hypokalemic alkalosis, normomagnesemia, hypercalciuria, and hyperaldosteronism. The clinical and laboratory findings were in accordance with Bartter syndrome. He has been followed up for 6 months and has suffered no further paralytic attacks under indomethacin therapy. This case highlights the importance of blood pH measurement in patients with hypokalemic periodic paralysis; it might prevent misdiagnosis and mismanagement in such diseases.
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PMID:Case of Bartter syndrome presenting with hypokalemic periodic paralysis. 1690 32


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