title: Pseudohypoaldosteronism type 1 due to novel variants of SCNN1B gene.
abstract: Autosomal recessive pseudohypoaldosteronism type 1 (PHA1) is a rare disorder characterized by sodium wasting, failure to thrive, hyperkalemia, hypovolemia and metabolic acidosis. It is due to mutations in the amiloride-sensitive epithelial sodium channel (ENaC) and is characterized by diminished response to aldosterone. Patients may present with life-threatening hyperkalemia, which must be recognized and appropriately treated. A 32-year-old female was referred to the National Institutes of Health (NIH) for evaluation of hyperkalemia and muscle pain. Her condition started in the second week of life, when she was brought to an outside hospital lethargic and unresponsive. At that time, she was hypovolemic, hyperkalemic and acidotic, and was eventually treated with sodium bicarbonate and potassium chelation. At the time of the presentation to the NIH, her laboratory evaluation revealed serum potassium 5.1 mmol/l (reference range: 3.4-5.1 mmol/l), aldosterone 2800 ng/dl (reference range: ≤21 ng/dl) and plasma renin activity 90 ng/ml/h (reference range: 0.6-4.3 ng/ml per h). Diagnosis of PHA1 was suspected. Sequencing of the SCNN1B gene, which codes for ENaC, revealed that the patient is a compound heterozygote for two novel variants (c.1288delC and c.1466+1 G>A), confirming the suspected diagnosis of PHA1. In conclusion, we report a patient with novel variants of the SCNN1B gene causing PHA1 with persistent, symptomatic hyperkalemia.
  
  
  CONCLUSIONS
  PHA1 is a rare genetic condition, causing functional abnormalities of the amiloride-sensitive ENaC.PHA1 was caused by previously unreported SCNN1B gene mutations (c.1288delC and c.1466+1 G>A).Early recognition of this condition and adherence to symptomatic therapy is important, as the electrolyte abnormalities found may lead to severe dehydration, cardiac arrhythmias and even death.High doses of sodium polystyrene sulfonate, sodium chloride and sodium bicarbonate are required for symptomatic treatment.
authors.affiliation: Department of Medicine, Columbia University Medical Center , New York, New York, 10032 , USA.
authors.forename: Yael R
authors.initials: YR
authors.lastname: Nobel
authors.affiliation: Section on Endocrinology and Genetics, Program on Developmental Endocrinology and Genetics, Eunice Kennedy Shriver National Institute of Child Health and Human Development, National Institutes of Health , Bethesda, BG 10-CRC, Room 1-3216, 10 Center Drive, Bethesda, Maryland, 20814 , USA.
authors.forename: Maya B
authors.initials: MB
authors.lastname: Lodish
authors.affiliation: Section on Endocrinology and Genetics, Program on Developmental Endocrinology and Genetics, Eunice Kennedy Shriver National Institute of Child Health and Human Development, National Institutes of Health , Bethesda, BG 10-CRC, Room 1-3216, 10 Center Drive, Bethesda, Maryland, 20814 , USA.
authors.forename: Margarita
authors.initials: M
authors.lastname: Raygada
authors.affiliation: Medical Oncology Branch, National Cancer Institute, National Institutes of Health , 10 Center Drive, Building 10, Room 12N-226, Bethesda, Maryland, 20892 , USA.
authors.forename: Jaydira Del
authors.initials: JD
authors.lastname: Rivero
authors.affiliation: Section on Endocrinology and Genetics, Program on Developmental Endocrinology and Genetics, Eunice Kennedy Shriver National Institute of Child Health and Human Development, National Institutes of Health , Bethesda, BG 10-CRC, Room 1-3216, 10 Center Drive, Bethesda, Maryland, 20814 , USA.
authors.forename: Fabio R
authors.initials: FR
authors.lastname: Faucz
authors.affiliation: Section on Endocrinology and Genetics, Program on Developmental Endocrinology and Genetics, Eunice Kennedy Shriver National Institute of Child Health and Human Development, National Institutes of Health , Bethesda, BG 10-CRC, Room 1-3216, 10 Center Drive, Bethesda, Maryland, 20814 , USA.
authors.forename: Smita B
authors.initials: SB
authors.lastname: Abraham
authors.affiliation: Section on Endocrinology and Genetics, Program on Developmental Endocrinology and Genetics, Eunice Kennedy Shriver National Institute of Child Health and Human Development, National Institutes of Health , Bethesda, BG 10-CRC, Room 1-3216, 10 Center Drive, Bethesda, Maryland, 20814 , USA.
authors.forename: Charalampos
authors.initials: C
authors.lastname: Lyssikatos
authors.affiliation: Section on Endocrinology and Genetics, Program on Developmental Endocrinology and Genetics, Eunice Kennedy Shriver National Institute of Child Health and Human Development, National Institutes of Health , Bethesda, BG 10-CRC, Room 1-3216, 10 Center Drive, Bethesda, Maryland, 20814 , USA.
authors.forename: Elena
authors.initials: E
authors.lastname: Belyavskaya
authors.affiliation: Section on Endocrinology and Genetics, Program on Developmental Endocrinology and Genetics, Eunice Kennedy Shriver National Institute of Child Health and Human Development, National Institutes of Health , Bethesda, BG 10-CRC, Room 1-3216, 10 Center Drive, Bethesda, Maryland, 20814 , USA.
authors.forename: Constantine A
authors.initials: CA
authors.lastname: Stratakis
authors.affiliation: Section on Endocrinology and Genetics, Program on Developmental Endocrinology and Genetics, Eunice Kennedy Shriver National Institute of Child Health and Human Development, National Institutes of Health, Bethesda, BG 10-CRC, Room 1-3216, 10 Center Drive, Bethesda, Maryland, 20814, USA; Johns Hopkins University School of Medicine, Division of Endocrinology, Diabetes, and Metabolism, Baltimore, Maryland, 21287, USA; Suburban Hospital, Bethesda, Maryland, 20814, USA.
authors.forename: Mihail
authors.initials: M
authors.lastname: Zilbermint