Effect of age and affection status on blood pressure, serum potassium and stature in familial hyperkalaemia and hypertension.
BACKGROUND
The rare autosomal dominant genetic disorder familial hyperkalemia and hypertension which is caused by mutations in WNK4 kinase, is characterized by childhood hyperkalemia and hypercalciuria, and appearance of hypertension in the third to fourth decade. Accompanying short stature is often described.


METHODS
We determined height, blood pressure and blood and urinary biochemical parameters in members of a very large family of FHHt with the WNK4 Q565E mutation.


RESULTS
The family has 57 members, 30 of whom (including 14 children) are affected. Prehypertension occurred in 7/11 affected and 1/10 unaffected children (P = 0.024). Serum potassium (SK) was ~0.5 mmol/L higher in affected children vs adults [5.98 ± 0.42 vs 5.46 ± 0.40 mmol/L, respectively (P < 0.0001)] (33 samples from 11 children and 36 samples from eight adults). SK of ≥ 6.0 mmol/L occurred in 16/33 children's samples and in 3/36 adults' samples (P = 0.0003). Hyperkalaemia in children is currently untreated. Children also had more severe hyperchloraemia and hypercalciuria. The family contains four large subfamilies, and each includes 8-10 siblings. In one subfamily, height Z-score was lower in affected vs unaffected subjects [- 2.69 ± 0.36 vs -1.05 ± 0.16, respectively (P < 0.0001)]. In the other three subfamilies, no such difference was found.


CONCLUSIONS
Short stature is not part of FHHt with the WNK4 Q565E mutation. Children affected with FHHt have a high prevalence of prehypertension, and their hyperkalaemia is more severe than that of affected adults. Children may have a more severe defect in the basic mechanism that produces hyperkalaemia. We suggest that, in affected adults, the attenuation of hyperkalaemia and appearance of hypertension may be the result of a late rise in the activity of renal transporters or channels such as the epithelial sodium channel.
Pediatric Endocrinology and Diabetes Unit, Safra Children’s Hospital Sheba Medical Center, Sackler School of Medicine, Tel Aviv University, Tel Hashomer 52621, Israel. farfel@post.tau.ac.il
Alon
A
Farfel
Haim
H
Mayan
Semyon
S
Melnikov
Eliezer J
EJ
Holtzman
Orit
O
Pinhas-Hamiel
Zvi
Z
Farfel
D000293:Adolescent; D000328:Adult; D000367:Age Factors; D001794:Blood Pressure; D001827:Body Height; D002648:Child; D002675:Child, Preschool; D005260:Female; D006801:Humans; D006947:Hyperkalemia / Q000503:physiopathology*; D006973:Hypertension / Q000503:physiopathology*; D008297:Male; D008875:Middle Aged; D009154:Mutation / Q000235:genetics; D010375:Pedigree; D011188:Potassium / Q000097:blood*; D058246:Prehypertension / Q000503:physiopathology*; D011379:Prognosis; D017346:Protein Serine-Threonine Kinases / Q000235:genetics; D055815:Young Adult
D017346:Protein Serine-Threonine Kinases; C433806:WNK4 protein, human; D011188:Potassium