Erythrocyte Na+,K+-ATPase and nasal potential in pseudohypoaldosteronism

OBJECTIVES: Pseudohypoaldosteronism type 1 (PHA1) is a rare inherited disorder characterized by salt-wasting due to target organ unresponsiveness to mineralocorticoids. PHA1 comprises two clinically and genetically distinct entities; isolated renal and systemic forms. DESIGN: The aim of this study was to investigate red blood cell (RBC) Na+,K+-ATPase activity and nasal potential difference (PD) in two pairs of unrelated dyzygous twins; one with the systemic form of the disease (PHA1-S) and the second with the isolated renal form (PHA1-R). Total and ouabain-sensitive ATPase activities were measured spectrophotometrically by a method that couples ATP hydrolysis with NADH oxidation. Maximal PD and response to amiloride perfusion were evaluated by a standard technique. RESULTS: In the twins with PHA1-S, persistently low activity of RBC Na+,K+-ATPase was found during a 6-year follow-up. Normalization of plasma renin activity (PRA) and plasma aldosterone was observed at the end of the first year of life. Maximal nasal PD was low and there was no significant response to amiloride. In the twins with PHA1-R, RBC Na+,K+-ATPase activity was very low at the time of diagnosis and normalized at the age of 6-8 months. PRA reverted gradually to normal values, whereas aldosterone levels remained high during the 6 years of follow-up. Maximal nasal PD and response to amiloride were normal. CONCLUSIONS: The observed differences in RBC Na+,K+-ATPase activity and nasal PD response to amiloride between the two pairs of twins support the contention of different basic pathogenic mechanisms in the two forms of PHA1.