Laboratory for Molecular Diagnostics
Center for Nephrology and Metabolic Disorders

Pseudohypoaldosteronism type 2

Pseudohypoaldosteronism type 2 is characterized by metabolic acidosis and hyperkalemia as usual. It differs in low renin and usually normal aldosteron levels and hypertension. The mode of inheritance is autosomal dominant.

Clinical Findings

Inheritance of Pseudohypoaldosteronism type 2 is autsomal dominant. As in all kinds of hypoaldosteronism metabolic acidosis and hyperkalemia are present. In contrast to othe other forms renin is suppressed but aldosteron is usually normal. Hight blood pressure is typical. Pathognomonic and of therapeutic relevance is prompt responsiveness to thiazide.

Diagnosis

In pseudohypoaldosteronism measurements of blood gases, serum electrolytes (Na, K, Cl), renin, and aldosterone are required. The diagnosis is made based on low renin and normal aldosterone levels. Blood pressure is elevated. Furthermore, the adequate respons to aldosterone may be tested. The correction of all abnormalities by low dose thiazide can is pathonomonic.

Pathogenesis

Mutations in two members of the WNK serine-threonine kinase family (WNK1 and WNK4) are known to cause the disease though still not understood is the precise pathogenic mechanisms. The protein product of these two genes is dentified in the distal convoluted tubule (DCT) and cortical collecting duct (CCD). The extracellular portion is found close to the tight junctions. There is an other locus on chromosome 1 (1q31-q42) associated with this disease. The gene still waits to become identified.

Systematic

Pseudohypoaldosteronism
Pseudohypoaldosteronism type 2
CUL3
KLHL3
WNK1
WNK4
Pseudohypoaldosteronism type1

References:

1.

None (2003) Mendelian forms of human hypertension and mechanisms of disease.

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2.

Sumara I et al. (2007) A Cul3-based E3 ligase removes Aurora B from mitotic chromosomes, regulating mitotic progression and completion of cytokinesis in human cells.

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3.

Rondou P et al. (2008) BTB Protein KLHL12 targets the dopamine D4 receptor for ubiquitination by a Cul3-based E3 ligase.

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4.

Kigoshi Y et al. (2011) Ubiquitin ligase activity of Cul3-KLHL7 protein is attenuated by autosomal dominant retinitis pigmentosa causative mutation.

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5.

Boyden LM et al. (2012) Mutations in kelch-like 3 and cullin 3 cause hypertension and electrolyte abnormalities.

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6.

Jin L et al. (2012) Ubiquitin-dependent regulation of COPII coat size and function.

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7.

Kipreos ET et al. (1996) cul-1 is required for cell cycle exit in C. elegans and identifies a novel gene family.

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8.

Michel JJ et al. (1998) Human CUL-1, but not other cullin family members, selectively interacts with SKP1 to form a complex with SKP2 and cyclin A.

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9.

Du M et al. (1998) Cloning and expression analysis of a novel salicylate suppressible gene, Hs-CUL-3, a member of cullin/Cdc53 family.

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10.

Ishikawa K et al. (1998) Prediction of the coding sequences of unidentified human genes. X. The complete sequences of 100 new cDNA clones from brain which can code for large proteins in vitro.

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11.

None (2005) Mineralocorticoid resistance.

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12.

OMIM.ORG article

Omim 145260 [^]
13.

Orphanet article

Orphanet ID 757 [^]
Update: April 29, 2019