Pseudohypoaldosteronism type 1: management issues.

We report a newborn girl with life-threatening hyperkalemia and salt wasting crisis due to severe autosomal recessive multiple target organ dysfunction pseudohypoaldosteronism type 1 (MTOD PHA1). She was aggressively managed with intravenous fluids, potassium-lowering agents, high-dose sodium chloride supplementation and peritoneal dialysis. Genetic analysis revealed a homozygous mutation of the α- ENaC (epithelial Na(+) channel) gene. She had a stormy clinical course with refractory hyperkalemia and prolonged hospitalization. Eventually, she succumbed to pneumonia and septicemia at 4 months of age. This is probably the first case of PHA1 confirmed by genetic analysis from India.

Clinical and molecular analysis of six Japanese patients with a renal form of pseudohypoaldosteronism type 1.

Pseudohypoaldosteronism type 1 (PHA1) is a rare condition characterized by neonatal salt loss with elevated plasma aldosterone and renin levels. Two types of PHA1 have been described: an autosomal recessive systemic form and an autosomal dominant renal form, in which the target organ defect is confined to the renal tubules. The dominant renal form of PHA1 is caused by heterozygous mutations in the NR3C2 gene, which encodes the mineralocorticoid receptor (MR). We determined clinical and biochemical parameters in two familial and four sporadic Japanese patient and analyzed the status of the NR3C2 gene. Failure to thrive was noted in five of the six patients. In one of the familial cases, the mother had an episode of failure to thrive when she was a toddler, but received no medical treatment. NaCl supplementation was discontinued in four of the six patients after they reached one year of age and they have grown normally thereafter. However, in one patient, 9 g/day of salt has been required to maintain serum Na concentration after 1 year of age. Analysis of NR3C2 identified three novel mutations [c. C1951T (p.R651X), c.304_305delGC (p.A102fsX103), c.del 603A (p.T201fsX34)] and one previously reported mutation [c.A2839G (p.947X)]. p.R651X was identified in one familial case and one unrelated sporadic patient. The patient who has been supplemented with large amount of salt was heterozygous for c.del 603A in exon 2. In conclusion, our study expands the spectrum of phenotypes, and characterized mutations of NR3C2 in the renal form of PHA1.

Life threatening hyperkalemia in a neonate with pseudo-hypoaldosteronism.

Pseudohypoaldosteronism type 1 is a rare disorder characterized by renal resistance to aldosterone which may present with a salt wasting crisis in infancy. We report a neonate with hyponatremia, severe dehydration and refractory life threatening hyperkalemia who was treated with dietary sodium chloride supplementation, potassium binding resins and fluid replacement therapy which proved to be lifesaving.

Critical points in the management of pseudohypoaldosteronism type 1.

Pseudohypoaldosteronism type 1 (PHA-1, MIM #264350) is caused by defective transepithelial sodium transport. Affected patients develop life-threatening neonatal-onset salt loss, hyperkalemia, acidosis, and elevated aldosterone levels due to end-organ resistance to aldosterone. In this report, we present a patient diagnosed as PHA-1 who had clinical and laboratory findings compatible with the diagnosis and had genetically proven autosomal recessive PHA-1. The patient received high doses of sodium supplementation and potassium-lowering therapies; however, several difficulties were encountered in the management of this case. The aim of this presentation was to point out the potential pitfalls in the treatment of such patients in the clinical practice and to recommend solutions.

Case report: severe neonatal hyperkalemia due to pseudohypoaldosteronism type 1.

Hyponatremia and hyperkalemia in infancy can represent a variety of renal and genetic disorders with significant long-term health implications. We report a newborn with severe hyperkalemia and hyponatremia from autosomal recessive pseudohypoaldosteronism type 1 requiring aggressive therapy. The evaluation and treatment of children with disorders of mineralocorticoid action are discussed.

[Multiple type I pseudohypoaldosteronism: neonatal management and outcome]. / Seudohipoaldosteronismo tipo I múltiple: presentación y seguimiento.

UNLABELLED: Multiple type I pseudohypoaldosteronism (PHA-I) is an autosomal recessive condition with multiple target-organ unresponsiveness to aldosterone, manifested early after birth with severe salt-wasting and hyperkalemia. Case 1. Female infant born at term after an uneventful pregnancy. One female sibling died in the first week of life with hyperkalemia. The diagnosis of multiple PHA-I resulted from a picture of dehydratation, hyperkalemia and hyponatremia with increased plasma renin activity (PRA), plasma aldosterone and sweat electrolytes. The treatment consisted of salt and sodium bicarbonate supplements, restricted potassium intake, cation exchange resins and high fluid intake. During first year she was hospitalized for severe salt-losing crises. At 7 years of age, she needs salt and sodium bicarbonate supplements and cation exchange resins. She has a normal growth and neurodevelopment. Case 2. Seven-day female newborn with consanguinity in maternal family. Pregnancy and delivery were uncomplicated. On admission she was severely dehydrated with hyponatremia, hyperkalemia, metabolic acidosis and elevated PRA, plasma aldosterone and sweat electrolytes. She remained hospitalized for six months and she was dependent on high amounts of salt and sodium bicarbonate supplements, fluid intake and cation exchange resins. Growth and neurodevelopment are normal. CONCLUSIONS: Multiple PHA-I may be suspected in a newborn with salt-loss and hyperkalemia without glucocorticoid defect. The frequent episodes of dehydratation during the first year of life require long hospitalization. The improvement with age make possible an ambulatory control after the first year of life.