ESPE Abstracts

Background: Pseudohypoaldosteronism type II (PHAII), is a rare renal tubular disease with an autosomal dominant inheritance characterized by hyperkalemic, hyperchloremic acidosis and hyporeninemia. Mutations in WNK4 and WNK1 were found initially. Recently have shown that KLHL3 and CUL3 are also causative genes.

Objective and hypotheses: Hypertension, an essential symptom of PHAII, manifest in adolescents and young adults. In the absence of family history the disease may remain undiagnosed in infancy and childhood. Manifestations such as hyperkalemia may also be overlooked.

Results: We evaluated two families with 23 subjects. PHAII was diagnosed in ten patients. The index cases were twin brothers and an infant. All patients carried a heterozygous mutation in KLHL3 (Q309R and R528H) gene. Family I: Identical twins, presented at age 8 years, because of short stature. Investigations revealed persistent hyperkalemia (6.4–7.1 mmol/l) in both. Three years of follow-up in another medical center failed to diagnose PHAII. Family history of hyperkalemia (the mother) and hypertension (mother, maternal grandmother) were overlooked. A sister, mother and maternal grandmother carried the same mutation. Family II: A 2 years old male born by Cesarean section after 38 week of gestation. B.W.: 3400 g. Four hours after birth he developed respiratory distress requiring ventilation. At age of seven days, he had hyperkalemia (7.0 mmol/l) and hyperchloremia (110 mmol/l) that persisted. Plasma renin activity (PRA) was <0.3 ng/ml per h. Hypertension appeared at 17 months of age (146/95 mm Hg). Thiazide diuretics normalized hyperkalemia and blood pressure. At age 2 years, mutation analysis revealed KLHL3 mutation. Three of four sisters (8, 13, 15 years old) and the mother also carried the mutation. All had hyperkalemia, hyperchloremia and acidosis. Except one, all had very low PRA. Sistolic blood pressure was elevated in all (>95 P).

Conclusions: To diagnose PHAII in pediatric age group high index of suspicion is required. Early diagnosis is crucial for appropriate therapy (thiazides) and genetic counseling.