Familial Hyperkalemic Hypertension: A New Early-onset Pediatric Case

The Familial hyperkalemic hypertension (FHHt) syndrome (OMIM #145260), first described in 1964, and also known as Gordon’s syndrome or pseudohypoaldosteronism type II (PHA II), is a rare autosomal dominant disease characterized by hypertension, hyperkalemia, hyperchloremic metabolic acidosis, and normal renal and adrenal function, with suppressed plasma rennin activity. Thiazides correct the metabolic abnormalities and hypertension (1–3). FHHt syndrome may be due to mutations in the WNK1 and WNK4 genes, encoding the with-nolysine kinases 1 and 4 respectively. WNK4 mutants fail to inhibit the thiazide-sensitive Na-Cl cotransporter (NCC), increasing reabsorption of chloride in the distal collecting tubule and causing volume expansion and hypertension, and fail to inhibit the ROMK1 channel, causing hyperkalemia. WNK1 mutants also cause an increase in chloride adsorption both through the activation of EnaC and reduced inhibition of NCC through its influence on the WNK4 activity (4–6). Three loci associated with FHHt have been identified (12p13.3 and 17p11-q21 and 1q31-q42), but other loci, not yet identified, are probably involved, demonstrating the genetic heterogeneity of FHH. The syndrome has been described primarily in adolescents and young adults, and in most cases, hypertension has been the presenting symptom; however, the investigations performed in the relatives of patients with the FHHt syndrome, showed that the metabolic disorders preceded hypertension, and no relationship between the severity of biochemical abnormalities and severity of hypertension was observed (7, 8). Short stature, hypercalciuria with urolithiasis and dental abnormalities have also been reported. The longterm prognosis remains uncertain because follow-up data are still limited.