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A Review of Pseudohypoaldosteronism Type 1

Pseudohypoaldosteronism Type 1 presents as severe neonatal salt wasting, with hyponatremia, hyperkalemia, dehydration, and metabolic acidosis despite a high plasma aldosterone. There are two forms. The Autosomal Dominant form affects kidneys only, and is due to a defect in aldosterone receptor. The Autosomal Recessive form affects the kidneys, colon, sweat, salivary glands, and lungs, and is due to mutations in genes coding for the amiloride-sensitive epithelial sodium channel.

Hanukoglu (J Pediatr1994) reported 4 patients with pseudohypoaldosteronism type 1: an 8-year-old girl with frequent episodes of cough and crackles in the chest, who had an FEV1 of 91% predicted; an 8 year old girl with recurrent lower respiratory tract infections and left lower lobe pneumonia but normal pulmonary functions; and twin 4-month-old boys with recurrent episodes of lower respiratory tract infection and wheezing. The cases had sweat chlorides ranging from 70 to 182. The authors noted that in general, up to 4 years of age, respiratory infections usually occurred at times of dehydration. Later in life, the patients' main symptoms were moderately severe cough, wheezing, and crackles.

Marthensen (Acta Paediatrica 1998) described a 6-year-old male with pseudohypoaldosteronism type 1. He had a sweat chloride of 110, and a history of recurrent bronchopneumonia associated with dehydration. Since 18 months of age, sputum cultures were positive for Pseudomonas aeruginosa. However, a CT of his chest showed no evidence of bronchiectasis, and his pulmonary function tests were normal. He was treated with chest physiotherapy and inhaled antibiotics. In a letter, Garty (Acta Paediatr 1999) described a 9 month old female with pseudohypoaldosteronism type 1, bronchopneumonia, and recurrent Pseudomonas aeruginosa otitis, conjunctivitis, and dermatitis. Schaedel (J Pediatr 99) postulated that an increase in the sodium concentration in the airway surface liquid promoted growth of Pseudomonas, and reduced killing of this organism. Elaine MacLaughlin (North American CF Conference, Pediatr Pulmonol 1996) noted the similarities between CF and pseudohypoaldosteronism type 1, in terms of pulmonary bacterial infection and sweat chloride concentration.

Effect on the Nasal Potential Difference
Prince (J Pediatr 1999) measured the nasal potential in a 5 day old infant with pseudohypoaldosteronism type 1, who presented with jaundice and a severe electrolyte derangement. The patient had a sweat chloride of 152, and CFTR mutation screening was negative. The patient's nasal potential difference determinations revealed an elevated basal potential difference, a normal response to chloride-free solution containing terbutaline, and no response to amiloride.

The Epithelial Sodium Channel (ENaC)
The Epithelial Sodium Channel (EnaC) contains 2 alpha (on chromosome 12), 1 beta, and 1 gamma subunit (on chromosome 16). ENaC controls sodium resorption in the kidneys and colon, and fluid secretion in lungs.

ENaC Mutations
Schaedel (J Ped 1999) looked for ENaC mutations in 4 patients with pseudohypoaldosteronism type 1 and negative CFTR gene analyses; a 2-year-old girl with recurrent bronchopneumonia, an 8 year old boy with frequent pneumonia colonized with Pseudomonas aeruginosa, normal pulmonary function tests and a normal resting nasal potential difference, his deceased 7 week old brother, and a 9 year old boy with recurrent bronchopneumonia. All four patients had mutations of the ENaC alpha-subunit (1449delC, 729delA, C1685->T). The authors suggested that mutations of the alpha-subunit of ENaC may be more likely to lead to lung disease in patients with pseudohypoaldosteronism type 1.

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