Atilla Cayir1, Yasar Demirelli2, Duran Yildiz2, Hasan Kahveci2, Oguzhan Yarali3, Erdal Kurnaz4, Doğuş Vuralli5, Huseyin Demirbilek5. 1. Department of Paediatric Endocrinology, Erzurum Regional Research and Training Hospital, Erzurum, Turkey, dratillacayir@gmail.com. 2. Department of Neonatology, Erzurum Regional Research and Training Hospital, Erzurum, Turkey. 3. Department of Medical Genetics, Erzurum Regional Research and Training Hospital, Erzurum, Turkey. 4. Department of Paediatric Endocrinology, Erzurum Regional Research and Training Hospital, Erzurum, Turkey. 5. Department of Paediatric Endocrinology, Hacettepe University Faculty of Medicine, Ankara, Turkey.
Abstract
OBJECTIVE: The systemic form of pseudohypoaldosteronism type 1 (PHA1) is an autosomal recessive disorder characterized by defective sodium transport in multi-organ systems. Mutations in the genes encoding the amiloride-sensitive epithelial sodium channel, ENaC, account for genetic causes of systemic PHA1. We describe systemic PHA1 due to 4 novel variants detected in SCNN1A and SCNN1B in 3 cases from 3 unrelated consanguineous families. PATIENTS AND METHODS: We evaluated the clinical presentations, biochemical and hormonal characteristics, and molecular genetic analysis results of 3 patients from 3 unrelated consanguineous families and parents from whom samples were available. RESULTS: The ages at presentation were postnatal days 9, 10, and 5. The main presentation symptoms were vomiting, poor feeding, weakness, weight loss, and skin rash. All patients exhibited laboratory characteristics including severe hyponatremia, hyperkalemia, metabolic acidosis, elevated plasma renin, elevated aldosterone, and positive sweat tests, suggesting a diagnosis of systemic PHA1. Molecular genetic analysis revealed 2 novel pathogenic variants [c.87C>A(p.Tyr29*)/IVS9 + 1G>A (c.1346 + 1G>A)] in SCNN1Bin case 1, a novel homozygous pathogenic variant [p.His69Arg(c.206A>G] in SCNN1Ain case 2, and a homozygous one-base duplication, p.A200Gfs*6 (c.598dupG), in SCNN1A in case 3. CONCLUSION: PHA1 should be considered at differential diagnosis in patients presenting with hyponatremia, hyperkalemia, and metabolic acidosis. The cases in this report involving 4 novel variants will add valuable insights into the phenotype-genotype relationship and will expand the mutation database.
OBJECTIVE: The systemic form of pseudohypoaldosteronism type 1 (PHA1) is an autosomal recessive disorder characterized by defective sodium transport in multi-organ systems. Mutations in the genes encoding the amiloride-sensitive epithelial sodium channel, ENaC, account for genetic causes of systemic PHA1. We describe systemic PHA1 due to 4 novel variants detected in SCNN1A and SCNN1B in 3 cases from 3 unrelated consanguineous families. PATIENTS AND METHODS: We evaluated the clinical presentations, biochemical and hormonal characteristics, and molecular genetic analysis results of 3 patients from 3 unrelated consanguineous families and parents from whom samples were available. RESULTS: The ages at presentation were postnatal days 9, 10, and 5. The main presentation symptoms were vomiting, poor feeding, weakness, weight loss, and skin rash. All patients exhibited laboratory characteristics including severe hyponatremia, hyperkalemia, metabolic acidosis, elevated plasma renin, elevated aldosterone, and positive sweat tests, suggesting a diagnosis of systemic PHA1. Molecular genetic analysis revealed 2 novel pathogenic variants [c.87C>A(p.Tyr29*)/IVS9 + 1G>A (c.1346 + 1G>A)] in SCNN1Bin case 1, a novel homozygous pathogenic variant [p.His69Arg(c.206A>G] in SCNN1Ain case 2, and a homozygous one-base duplication, p.A200Gfs*6 (c.598dupG), in SCNN1A in case 3. CONCLUSION:PHA1 should be considered at differential diagnosis in patients presenting with hyponatremia, hyperkalemia, and metabolic acidosis. The cases in this report involving 4 novel variants will add valuable insights into the phenotype-genotype relationship and will expand the mutation database.
Authors: Ali S Alzahrani; Meshael Alswailem; Bassam Bin Abbas; Ebtesam Qasem; Afaf Alsagheir; Azza Al Shidhani; Aisha Al Sinani; Maryam Al Badi; Ali Al-Maqbali; Manal Al Shawi; Abdulhameed Albunyan; Abdulghani Bin Nafisah; Yufei Shi Journal: J Endocr Soc Date: 2021-05-17