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A Review of Pseudohypoaldosteronism Type 1
Types
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.
Manifestations
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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