Original article Severe pseudohypoaldosteronism in a pair of twins not associated with hydramnios T. Bistritzer 1 , E. Lahat 1 , G. Eshel 1 , J. Barr 1 , A. Hanukoglu 2 , and M. Aladjem 1 1 Department of Pediatrics, Assaf Harofeh Medical Center, Sackler Faculty of Medicine, Tel Aviv University, Israel 2 Department of Pediatrics, Edith Wolfson Medical Center, Sackler Faculty of Medicine, Tel Aviv University, Israel Received December 13, 1994; received in revised form September 15, 1995; accepted October 6, 1995 Abstract. A pair of non-identical twins with severe pseu- dohypoaldosteronism (PHA) were followed over a period of 4 years. The diagnosis was based on dehydration, hy- ponatremia, hyperkalemia, high urine sodium/potassium ratios, and high serum concentrations of aldosterone and renin. Sweat and saliva electrolyte concentrations were high, suggesting multifocal target-organ unresponsiveness to mineralocorticoids. No hydramnios was observed during pregnancy. Despite continuous treatment with sodium chloride and sodium bicarbonate ( 20 g/day) and cation exchange resin (Kayexalate, sodium polystyrene sulfonate, 4 g/kg per day), the children had repeated episodes of dehydration, hyponatremia, and hyperkalemia. Growth velocity was normal in both twins. Catch-up growth was observed following infancy in the first twin. Normalization of plasma aldosterone, electrolytes, and renin concentra- tions was achieved at the age of 9 months. Key words: Pseudohypoaldosteronism – Twins – Hydram- nios Introduction Pseudohypoaldosteronism (PHA) is a rare familial disease usually occurring in early infancy and characterized by salt wasting, hyponatremia, and hyperkalemia, despite high levels of plasma aldosterone. The patients are insensitive to mineralocorticoids. Electrolyte abnormalities can be cor- rected only by sodium supplementation [1]. Since the first description of a patient with PHA in 1958 by Cheek and Perry [2], about 70 additional patients have been reported [3]. Clinically, the disease varies in severity, being self limited in most instances and spontaneous re- mission occurs within the first 2 – 3 years of life [4 – 6]. A minority of patients may exhibit a protracted course with recurrent, life-threatening episodes of salt loss [7, 8]. Hy- dramnios has been reported in premature infants with PHA [9, 10]. We report a pair of twins with severe PHA char- acterized by multifocal target-organ unresponsiveness to mineralocorticoids and not associated with hydramnios. Patients and methods Methods Hormone levels were determined by commercial radioimmunoassay kits: aldosterone, 17-hydroxyprogesterone (17-OHP), dehydroepian- drosterone sulfate (DHEA-S), and cortisol. Diagnostic Products (Los Angeles, Calif., USA); plasma renin activity (PRA), New England Nuclear (Boston, Mass., USA); testosterone, Zer Sci Based (Jerusalem, Israel). Sweat samples were collected by pilocarpine iontophoresis and saliva from the sublingual region. Patients The patients are a pair of male, non-identical twins born to Jewish parents – first cousins – of Iranian origin. Another male sibling with PHA died at 3 months of severe dehydration. The twins were born at 36 weeks’ gestation after an uncomplicated pregnancy and normal delivery; birth weights were 3.3 kg (twin 1) and 2.5 kg (twin 2). Re- peated ultrasound and fetal echocardiographic examinations during pregnancy were normal. At 5 days of age, they were hospitalized be- cause of vomiting, anorexia, and severe weight loss. The results of laboratory investigations are shown in Table 1. Increased sweat and saliva electrolyte concentrations suggested unresponsiveness to mineralocorticoids of the renal tubule, sweat and salivery glands. Congenital adrenal hyperplasia was excluded by normal plasma levels of 17-OHP, cortisol, testosterone, and DHEA- S. Ultrasonography of the adrenals and kidneys was normal in the first twin. Non-obstructive hydronephrosis was found in the second. The parents and two additional male siblings had normal values of PRA, aldosterone, and plasma and sweat electrolytes. Clinical course. Treatment with high-dose intravenous so- dium ( 20 g/day) as physiological saline and 7.5% sodium bicarbonate was initiated in both infants. Following nor- malization, both were switched to oral sodium chloride and Pediatr Nephrol (1996) 10: 438 – 441  IPNA 1996 Correspondence to: T. Bistritzer, Department of Pediatrics “B”, Assaf Harofeh Medical Center, Zerifin 703000, Israel