ESPE Abstracts (2015) 84 P-3-581

New Mutation Causing Systemic Pseudohypoaldosteronism

Stefania Pedicellia, Paola Cambiasoa, Maria-Christina Zennarob, Giusy Ferroa, Stefano Cianfarania,c & Marco Cappaa


aUnit of Endocrinology and Diabetes, Bambino Gesù Children’s Hospital, IRCCS, Rome, Italy; bDepartement de Génétique, Hôpital Européen Georges Pompidou, Paris, France; cDepartment of Women’s and Children’s Health, Karolinska Institutet, Stockholm, Sweden


Background: Pseudohypoaldosteronism (PHA) is a rare heterogeneous syndrome of mineralocorticoid resistance. PHA type 1 (PHA1) is characterized by neonatal salt loss, failure to thrive, dehydration and circulatory shock. It includes two forms: renal (autosomal dominant), due to mutations in mineralocorticoid receptor coding gene NR3C2, and systemic (autosomal recessive), due to mutations in subunit genes of the epithelial sodium channel (ENaC). ENaC is constituted of three subunits, coded by SCNN1A gene located on chromosome 12p13.31 (alpha subunit), SCNN1B and SCNN1G genes on chromosome 16p12.1 (β and γ subunits respectively). Due to the rarity of the disease, no genotype-phenotype correlations have been established. The systemic form usually presents in the neonatal period with salt loss from kidney, colon, sweat and salivary glands and can show pulmonary symptoms, similar to cystic fibrosis. It is a life-long disease without improvement over time, characterized by life-threatening salt-losing crises that require extensive sodium supplementation and potassium-lowering agents.

Case presentation: We report the case of a 6-months-old girl with systemic form of PHA1, presented in the neonatal period with dehydration, weight loss, feeding difficulties, hyperkalemia, hyponatremia, metabolic acidosis and elevated plasma aldosterone levels. Clinical conditions improved after elevated sodium and bicarbonathes supplementation, administration of ion exchange resins and nutrition with milk formula low in protein and electrolytes. Nevertheless, frequent salt-losing crises occurred, requiring electrolytes and fluids intravenously. She also presented conjunctivitis and an altered sweat test with disventilation pulmonary area secondary to thick secretion.

Conclusions: Genetic analysis showed a double heterozygosity in intron 8 of the SCNN1G gene: c.1294+5G>A (inherited from the father) and c.1295-10T>A (transmitted by the mother). The first mutation puts down the splicing site in 5’ and is probably pathogenetic; the second one abolishes the splicing site in 3’ and determines a cryptic splicing of unknown significance.

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