The clinical severity of Familial hyperaldosteronism type III (FH-III) is not solely determined by the KCNJ5 genotype, as a patient with the typically severe G151R mutation exhibited a mild, spironolactone-responsive phenotype.
Spironolactone may provide durable control in select FH-III; leaves open whether KCNJ5 genotype alone determines severity.
BACKGROUND: Familial hyperaldosteronism type III (FH-III) is a rare autosomal dominant disease for which five missense mutations in KCNJ5 have been identified. FH-III has a wide phenotypic variability from spironolactone-responsive hyperaldosteronism to massive adrenal hypertrophy with drug-resistant hypertension. This variation has mainly been attributed to genotype, because, in contrast to other genotypes (G151R, T158A, I157S, and Y152C), (1) FH-III patients with G151E have shown milder phenotype, and (2) G151E-harboring cells were found to have rapid lethality due to much larger sodium conductance of the encoded channel (Kir3.4), which prevents adrenal hypertrophy. METHODS: Here we describe the clinical course of a sporadic case of FH-III, with de novo G151R mutation. RESULTS: The patient developed polyuria at around 1.5 years of age and developed hypertension and hypokalemia by 4 years of age. Thereafter, spironolactone treatment successfully ameliorated hyperaldosteronism for 7 years with no discernible adrenal enlargement. CONCLUSION: Diverse clinical severity in FH-III cannot be defined solely by KCNJ5 genotype.
No takes yet. Share an insight, caveat, or question.
Adachi et al. (2014) studied this question.
Synapse has enriched 5 closely related papers on similar clinical questions. Consider them for comparative context: