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Erschienen in:
30.06.2020 | Clinical Quiz
A rare case of hyporeninemic hypertension: Answers
Erschienen in: Pediatric Nephrology | Ausgabe 3/2021
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All the conditions listed below result in volume expansion and subsequent suppression of renin secretion.
I.
Liddle’s syndrome: autosomal dominant inheritance, gain-of-function variants of SCNN1B or SCNN1G, encoding the beta and gamma subunits of the epithelial Na+ channel ENaC, respectively. This results in less channel ubiquitination, higher cell surface abundance of ENaC in the connecting tubule and collecting ducts, and more Na+ and water absorption [1, 2].
II.
Gordon syndrome (pseudohypoaldosteronism type 2): autosomal dominant inheritance, WNK1, WNK4, CUL1, and KLHL1 (KLHL1 is also inherited in an autosomal recessive manner). Clinical and laboratory characteristics include hyperkalemia, metabolic acidosis, and hypercalciuria. Large deletions within the first intron of the WNK1 gene result in increased WNK1 expression which stimulates NCC. KLHL3 and CUL3 are part of an ubiquitin-protein ligase complex which degrades WNKs. Loss-of-function variants in KLHL3 and CUL3 cause an increased abundance of WNK4 which stimulates NCC [3‐5]. Gain-of-function variants in WNK4 also increase NCC activity [5].
III.
Apparent mineralocorticoid excess (AME): autosomal recessive inheritance, due to inactivating variants of HSD11B2 encoding the 11β-hydroxysteroid dehydrogenase type 2 enzyme. Under normal circumstances, both aldosterone and cortisol bind to mineralocorticoid receptors (MR), but cortisol is 100-fold more abundant in the circulation than aldosterone [6]. This enzyme converts cortisol to the inactive hormone cortisone and thereby protects the MR from cortisol action. Inactivating mutations causes an excess of cortisol to bind to MR and MR stimulation in the collecting ducts leading to aldosterone-like effects [7].
IV.
Hypertension exacerbated by pregnancy: autosomal dominant inheritance, gain-of-function variants of MR resulting in higher sensitivity to non-mineralocorticoid steroids causing enhanced Na+ absorption in the distal nephron. The name of this disorder is misleading since the phenotype is not limited to pregnancy or females [8].
V.
Glucocorticoid remediable aldosteronism (GRA) or familial hyperaldosteronism type 1: autosomal dominant inheritance, due to an unequal crossover (nonallelic homologous recombination) between the genes encoding 11β-hydroxylase and aldosterone synthase. This creates a hybrid fusion gene containing an ACTH-responsive promoter and an aldosterone synthase coding region, which responds to ACTH [9].
VI.