Includes:
– Pseudohypoaldosteronism type 1, autosomal dominant – OMIM#177735 https://omim.org/entry/177735 – NR3C2 gene
Also known as: PHAIa; renal pseudohypoaldosteronism type; autosomal dominant PHAI
– Pseudohypoaldosteronism type 1, autosomal recessive – OMIM#264350 https://omim.org/entry/264350 – SCNN1A, SCNN1B, SCNN1G genes
Also known as: generalized pseudohypoaldosteronism type 1; PHA1b; autosomal recessive
1. The Disease:
A rare, primary form of mineralocorticoid resistance characterized by mild to profound salt wasting either restricted to the kidney (renal pseudohypoaldosteronism type 1), or generalized affecting many organs (generalized pseudohypoaldosteronism type 1).
2. The Symptoms:
Clinical presentation is in the neonatal period with failure to thrive, vomiting and dehydration with biochemical findings of hyperkalaemia, metabolic acidosis and, elevated plasma aldosterone and renin concentration. Lack of early signs or symptoms does not exclude the diagnosis. The two different forms can be distinguished at the clinical and genetic level:
- Renal PHA1 is the most frequent form and presents with mild mineralocorticoid resistance that is restricted to the kidneys and that usually improves in early childhood;
- Generalized PHA1 is a more severe form with salt wasting from multiple organs (including lung, kidney, colon, sweat and salivary glands) and persistence into adulthood. In both forms, presentation is in the neonatal period with a salt-losing syndrome, failure to thrive, vomiting and dehydration. The generalized form may present with respiratory involvement (including persistent rhinorrhea, infections, tachypnea, recurrent coughing and wheezing, and, less frequently, respiratory distress syndrome), and cutaneous lesions (caused by inflammation of eccrine structures). The clinical course may be complicated by cardiac dysrhythmias and cardiac arrest in generalized PHA1.
- Biological findings include hyponatremia, hyperkalaemia, metabolic acidosis, and inappropriately high urinary sodium excretion.
3. Actions to take in case of early diagnosis
- Babies with a positive genetic test for renal PHA1 present 1 mutation in the NR3C2 Instead, for generalized PHA1, babies present 2 different mutations or 1 mutation in homozygosis in the SCNN1A, SCNN1B or SCNN1G genes.
- Babies should continue breastfeeding
- Laboratory findings: presence of high plasma and urinary aldosterone and high plasma renin levels.
- The diagnosis is based on genetic and laboratorial results, familial history and clinical signs when present.
- Treatment consists in salt supplementation and rehydration and, where indicated, correction of hyperkalemia and acidosis. Salt supplementation is administered in accordance with disease severity. Symptomatic treatment is necessary for the respiratory tract illness and to correct the skin phenotype.
- Renal PHA1 improves with age and treatment can be discontinued after a variable period of time in most patients, generally around age 18-24 months. With age, patients compensate for the distal salt loss by up-regulating the mineralocorticoid receptor axis.
- Early diagnosis within the first week of life is critical to survival in patients with generalized PHA1. In this form, no remission has been reported and patients are prone to life-threatening episodes of salt loss into adulthood.
- 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:
Biblio: Furgeson SB, Linas S. Mechanisms of type I and type II pseudohypoaldosteronism. J Am Soc Nephrol. 2010;21(11):1842-1845. PMID: 20829405