Treatment of Bartter's syndrome with indomethacin

Two patients with Bartter's syndrome were treated with indomethacin (2 mg/kg/day). The administration of the drug resulted in weight gain; a decrease in the rate of urinary excretion of sodium and inorganic phosphate suggesting an increase in proximal tubular reabsorption; an increase in serum potassium concentration, with a transient decrease in the rate of urinary potassium excretion in one patient; and a decrease in plasma renin activity and in the rate of urinary aldosterone excretion. Since indomethacin has been shown to inhibit prostaglandin synthetase, these observations support the hypothesis that prostaglandin excess is a basic pathogenic mechanism in Bartter's syndrome.     

Treatment of Bartter's syndrome in early childhood with prostaglandin synthetase inhibitors.

The diagnosis of Bartter's syndrome was made in a 9-month-old boy investigated for poor weight and height gain. Initial treatment with oral potassium supplements and later spironolactone had little or no effect on his growth, although plasma potassium rose to normal after spironolactone. At 33 months indomethacin therapy was started with dramatic results. His symptoms went and his height and weight accelerated into the normal range. In view of the toxicity of indomethacin it was replaced after 12 months by another prostaglandin synthetase inhibitor, ketoprofen, with a satisfactory result. During the change-over period from indomethacin to ketoprofen the expected deterioration in clinical well-being was observed, accompanied by a rise in urinary prostaglandins and plasma renin activity. Prostaglandin synthetase inhibitors provide the best available treatment for Bartter's syndrome.     

The role of prostaglandins in Bartter's syndrome

In two children with Bartter's syndrome, treatment with indomethacin halved the urinary excretion of prostaglandins E and F within 24 hours and subsequently maintained it within the normal range during follow-up for more than 5 years. Growth rate was improved and plasma renin and aldosterone and the urinary excretions of sodium and calcium fell to normal. Both children continued to lose excessive quantities of potassium in the urine. The results provide further evidence that over-production of prostaglandins is not the primary cause of Bartter's syndrome.     

Familial Bartter's syndrome: report of a case with early manifestations and persistent hypercalciuria

A case of familial Bartter's syndrome is reported. The child had early and severe clinical and biochemical manifestations. Indomethacin treatment effectively controlled the increased prostaglandin excretion but corrected only partially the potassium and the calcium losses. The child developed during treatment high serum calcium levels which were associated with high parathyroid hormone and calcitriol serum levels.     

Acute nonlymphocytic leukemia after transient myeloproliferative disorder in a patient with Down syndrome

An infant with Down syndrome (DS) and RH isoimmunization developed transient myeloproliferative disorder (TMD) during the neonatal period. At 16 months she presented with acute nonlymphocytic leukemia (ANLL). Cytogenetic studies during TMD showed trisomy 21 only but new abnormalities emerged during ANLL. She is now in complete remission 5 years after diagnosis. Patients with TMD have either trisomy 21 or mosaic 21 in blood and bone marrow but in phenotypically normal children this cell line disappears with resolution of the TMD. A review of the literature indicates that there are no clinical, hematological, or cytogenetic differences between DS children with TMD who subsequently develop acute leukemia and those who do not. However, the leukemia in the former group may differ in presentation, type, and possibly survival time from other DS children who develop leukemia de novo.     

Bartter's syndrome in Arabic children: review of 13 cases

BACKGROUND: Bartter's syndrome (BS) is an inherited disease of renal potassium wasting characterized by hypokalemic alkalosis, normal blood pressure, vascular insensitivity to pressor agents and elevated plasma concentrations of renin and aldosterone. It is caused by generalized hyperplasia of the juxtaglomerular apparatus at the site of renin production caused by mutations in the Na-K-2Cl cotransporter gene, NKCC2. The objective of our study is to establish the prevalence and incidence of BS in Kuwait and to assess treatment modalities for it. METHODS AND RESULTS: Bartter's syndrome was diagnosed in 13 Kuwaiti children over a 14 year period (1981-1995) with the estimated incidence of 1.7/100,000 live births. The mean age at diagnosis was 9.3 months (range 2-32 months). There were five males and eight females (ratio 1:1.6). The mean duration of follow up was 5.6 years (1-14 years). Both consanguinity and familial history among our patients were high (69 and 54%, respectively). All patients had hypokalemia, hypochloremia with metabolic alkalosis, hyperreninemia and were normotensive. Clinical presentation was essentially similar to that in other series. Eleven patients (85%) had growth failure, two had nephrocalcinosis (15%) and one had renal failure. All patients were treated with supplemental potassium, an aldosterone antagonist (spironolactone) and a prostaglandin synthetase inhibitor (indomethacin or aspirin) sequentially. Significant catch-up of growth (four patients) and increases in serum potassium (eight patients) were recorded after administration of indomethacin therapy. One patient died of severe pneumonia with respiratory failure from hypokalemic myopathy. Clinical presentation, inheritance, complications and therapy of BS are briefly discussed. CONCLUSION: Bartter's syndrome is a rare disease, but should be considered in the differential diagnosis of other disorders with growth failure and/or hypokalemia. Early diagnosis, close follow up and compliance with treatment may lead to appropriate growth and development.     

Bardet-Biedl syndrome with syndrome X: a patient report

Bardet-Biedl syndrome (BBS) is an autosomal recessive condition with a wide spectrum of clinical features. The principal manifestations are rod-cone dystrophy (sometimes called atypical retinitis pigmentosa), postaxial polydactyly, central obesity, mental retardation, hypogonadism, and renal dysfunction. The clinical diagnosis of syndrome X defines a patient with abnormal glucose metabolism, hypertension, hyperlipidemia and obesity. We report here a 15 year-old girl with BBS presenting with syndrome X.     

Recovery of prostaglandin production associated with reopening of the ductus arteriosus after indomethacin treatment in preterm infants with respiratory distress syndrome

Increased PGE production has been demonstrated in 9 of 17 preterm infants with patent ductus arteriosus (PDA) associated with respiratory distress syndrome (RDS). Inhibition of PGE production in eight preterm infants with PDA and RDS was associated with marked improvement in the respiratory and circulatory function of all of them. However, in six of them this effect was only transient. In the posttreatment period of five and a half days reopening of the ductus arteriosus was frequently associated with increased PGE production and a drop of indomethacin serum levels. Three of these six infants were transferred for surgical ligation whereas the other three were successfully treated with a second course of indomethacin. However, the margin between closure of the ductus arteriosus and the deterioration of kidney function in preterm infants treated with a presently recommended indomethacin dosage was narrow. In conclusion, until an acceptable therapeutic serum level of indomethacin for ductal closure in preterm infants has been established and the duration of effective prostaglandin synthesis inhibition is known, it is too early for a general recommendation of a dosage regime of indomethacin for the pharmacological closure of PDA in infants with RDS.     

Lung transplantation in a patient with a thrombophilic disorder

Abstract:  The prothrombin G20210A mutation has been associated with an increased risk of graft failure in renal transplant recipients. Little is known about the potential effect of this mutation on lung transplant recipients. We report the case of bilateral lung transplantation in a patient with cystic fibrosis who was heterozygous for the G20210A mutation of the prothrombin gene.     

Clinical evidence of intrauterine disturbance in Prader-Willi syndrome, a genetically imprinted neurodevelopmental disorder

BACKGROUND: Imprinted genes are considered to play an important role in growth and early development but much of the research is based on animal studies. AIM: This study reports clinical data from a French population concerning prenatal, perinatal and postnatal complications in Prader-Willi syndrome (PWS), a genetically imprinted neurodevelopmental disorder associated with growth retardation, intellectual impairment and obesity. STUDY DESIGN: Data from family health records concerning prenatal, perinatal and postnatal complications were collected from 52 French people with the deletion form (DEL), and 34 French people with the maternal disomy form of PWS (UPD) and compared against national norms and between groups. RESULTS: Significant findings include: a history of miscarriage, high rate of polyhydramnios (12/34 UPD, 11/52 DEL), a high rate of induced labour, a high rate of Caesarian section (20/34 UPD, 26/52 DEL), small gestational age (10/34 UPD, 22/52 DEL), hypotonia (34/34 UPD, 49/52 DEL), and suckling deficit (25/34 UPD, 46/52 DEL). Significant differences between genetic subtypes include a higher rate of induced labour in UPD (27/34 UPD, 25/52 DEL), an increased risk of premature term in UPD (9/34 UPD vs. 4/52 DEL), raised maternal age in UPD (36.4 years vs. 29.3 years), low birth weight for newborns with a deletion form of PWS (girls 2.8 kg, boys 2.7 kg), a positive correlation between parental weight and offspring birth weight only for patients with UPD (UPD maternal: r=0.62, paternal: r=0.51). CONCLUSION: The results indicate significant intrauterine disturbance in PWS, particularly in PWS due to UPD, but a more significant weight disturbance for PWS due to deletion.