Pseudo hypoaldosteronism type 1B due to novel deletion mutation in SCNN1A gene

Noman Ahmad, Meshal Atiyah, Balgees Abdulhadi Al Ghamdi, Halah Faleh Al Enizi, Ali Saeed Al Zahrani


Pseudo hypoaldosteronism type 1B (PHA1B) is a systemic form of salt wasting. Children present after the first week of life with typical symptoms of an adrenal crisis. PHA1B is caused by autosomal recessive homozygous mutations in genes encoding epithelial sodium channels (ENaC) subunits α, β and γ. ENaC are widespread and present in renal tubules, airways, colon, sweat and salivary glands. Electrolyte imbalance is significant with severe hyponatremia, hyperkalemia and metabolic acidosis. In early life until approximately one year of age electrolytes remain unstable despite active management but then gradually improve. The mainstay of treatment is high dose salt replacement, sodium bicarbonate and sodium polystyrene therapy. The adequate treatment and monitoring can result in normal physical and psychomotor development. We present a case of PHA1B with severe intractable electrolyte imbalances in neonatal period. The genetic sequence revealed a novel homozygous deletion mutation in exon 4 of the SCNN1A gene (c.942delC, p.N315Tfs*16).


Epithelial sodium channels, Hyperkalemia, Hyponatremia, Metabolic acidosis, Pseudo hypoaldosteronism type 1B, SCNN1A gene

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Cheek DB, Perry JW. A salt wasting syndrome in infancy. Archi Dis Childhood. 1958 Jun;33(169):252-6.

Geller DS, Rodriguez-Soriano J, Boado AV, Schifter S, Bayer M, Chang SS, et al. Mutations in the mineralocorticoid receptor gene cause autosomal dominant pseudo hypoaldosteronism type I. Nature Genetics. 1998 Jul;19(3):279-81.

Kerem E, Bistritzer T, Hanukoglu A, Hofmann T, Zhou Z, Bennett W, et al. Pulmonary epithelial sodium-channel dysfunction and excess airway liquid in pseudo hypoaldosteronism. N Engl J Med. 1999 Jul 15;341(3):156-62.

Güran T, Değirmenci S, Bulut İK, Say A, Riepe FG, Güran Ö. Critical points in the management of pseudohypoaldosteronism type 1. J Clini Resea Pediatr Endocrinol. 2011 Jun;3(2):98.

Chang SS, Grunder S, Hanukoglu A, Rösler A, Mathew PM, Hanukoglu I, et al. Mutations in subunits of the epithelial sodium channel cause salt wasting with hyperkaliaemic acidosis, pseudo hypoaldosteronism type 1. Nature Genetics. 1996 Mar;12(3):248-53.

Welzel M, Akin L, Büscher A, Güran T, Hauffa BP, Högler W, et al. Five novel mutations in the SCNN1A gene causing autosomal recessive pseudo hypoaldosteronism type 1. Euro J Endocrinol. 2013 May 1;168(5):707-15.

Attia NA, Marzouk YI. Pseudo hypoaldosteronism in a neonate presenting as life-threatening hyperkalaemia. Case reports in endocrinol. 2016;2016.

Martin JM, Calduch L, Monteagudo C, Alonso V, Garcia L, Jorda E. Clinico‐pathological analysis of the cutaneous lesions of a patient with type I pseudohypoaldosteronism. J Euro Acad Dermatol Venereol. 2005 May;19(3):377-9.

Canessa CM, Merillat AM, Rossier BC. Membrane topology of the epithelial sodium channel in intact cells. Am J Physiol-Cell Physiol. 1994 Dec 1;267(6):C1682-90.

Schild L. The epithelial sodium channel and the control of sodium balance. Biochimica et Biophysica Acta (BBA)-Molecular Basis of Disease. 2010 Dec 1;1802(12):1159-65.

McDonald FJ, Yang B, Hrstka RF, Drummond HA, Tarr DE, McCray PB, et al. Disruption of the β subunit of the epithelial Na+ channel in mice: hyperkalaemia and neonatal death associated with a pseudo hypoaldosteronism phenotype. Proceedings of the Nat Acad Sci. 1999 Feb 16;96(4):1727-31.