Pseudohypoaldosteronism type 2

Baby Detect > Nephrology > Pseudohypoaldosteronism type 2

Includes:

– Pseudohypoaldosteronism type IIB – OMIM#614491

https://omim.org/entry/614491 – WNK4 gene

Also known as: PHA2B; autosomal dominant

– Pseudohypoaldosteronism type IIC – OMIM#614492

https://omim.org/entry/614492 – WNK1 gene

Also known as: PHA2C; autosomal dominant

– Pseudohypoaldosteronism type IID – OMIM#614495

https://omim.org/entry/614495 – KLHL3 gene

Also known as: familial hyperkalemic hypertension, PHA2D; autosomal dominant/ recessive

– Pseudohypoaldosteronism type IIE – OMIM#614496

https://omim.org/entry/6144956 – CUL3 gene

Also known as: familial hyperkalemic hypertension, PHA2D; autosomal dominant/ recessive

1. The Disease:

Pseudohypoaldosteronism type II (PHAII) is characterized by hyperkalemia despite normal glomerular filtration rate (GFR) and frequently by hypertension. Other associated findings in both children and adults include hyperchloremia, metabolic acidosis, and suppressed plasma renin levels. Aldosterone levels are variable, but are relatively low given the degree of hyperkalemia (elevated serum potassium is a potent stimulus for aldosterone secretion). Hypercalciuria is well described.

2. The symptoms:

Hypertension (blood pressure >140/90 mm Hg) generally manifesting in adolescence or adulthood but also reported in children. Lack of early signs or symptoms does not exclude the diagnosis.

  • Laboratory findings: hyperkalemia in the absence of impaired glomerular filtration – serum concentration of potassium ranges from mildly (serum K ~5.0-6.0 mmol/L) to severely increased (>8.0 mmol/L) [normal range: ~3.5-5.1 mmol/L]. This finding is nearly universal in affected individuals at all ages.
  • Metabolic acidosis: serum concentration of bicarbonate ranging from 14 to 24 mmol/L [normal range: ~22-29 mmol/L]
  • Hyperchloremia: serum concentration of chloride ranging from 105 to 117 mmol/L (normal range: ~99-108 mmol/L)
  • Suppressed plasma renin levels
  • Variable serum aldosterone levels that tend to be relatively suppressed in the context of hyperkalemia
  • Serum calcium and parathyroid hormone levels that are normal. However, hypercalciuria is noted in at least a subset of individuals.

Family history: A first-degree relative with similar findings. PHAII should be suspected in individuals with described clinical features, supportive laboratory findings, and family history. Lack of some of these items does not exclude the diagnosis.

3. Actions to take in case of early diagnosis

  • Babies identified with a heterozygous pathogenic variant in CUL3, WNK1 or WNK4 genes; or a heterozygous pathogenic variant or biallelic pathogenic variants (2 copies of a mutation or 1 copy in homozygosis in the KLHL3 gene).
  • Babies should continue breastfeeding
  • Search for the laboratory findings described.
  • The diagnosis is based on genetic and laboratorial results, familial history and clinical signs when present.
  • Electrolyte and blood pressure abnormalities of PHAII in children and adults are often corrected with thiazide diuretics.
  • Control of blood pressure is important to reduce the risk of cardiovascular and renal disease and stroke.
  • Agents/circumstances to avoid: Untreated individuals with PHAII should avoid excessive intake of foods high in salt and potassium as these may exacerbate hypertension and hyperkalemia.
  • Genetic counselling is highly recommended for family planning and evaluation of at-risk family members such as siblings as there are autosomal dominant and autosomal recessive forms.

4. For more information:

Orphanet:

Biblio: