Isolated hypoaldosteronism (IHA) is a rare (1/1.000.000) AR disorder caused by mutations in CYP11B2 gene and may result in life-threatening salt wasting and failure to thrive an. We presented this case because of the rareness of disease and our patient is only the second Turkish case with a genetically confirmed diagnosis.
A 3-day-old male first presented with jaundice and physical examination with normal findings. The parents are Turkish and consanguineous. Initial laboratory examinations showed hyponatremia (129 mEq/L) and hyperkalemia (6.9 mEq/L). Endocrinological evaluation showed low plasma aldosterone concentration of 40 pg/mL (50-900 pg/mL) and markedly elevated plasma renin activity (PRA) >200 ng/mL/hr (2.35-370 ng/mL/hr); cortisol level after adrenocorticotropic hormone stimulation was 31.5 ug/dL. He was started a fludrocortisone treatment as 0.1 mg/daily with IHA diagnosed. Fludrocortisone dose was raised to 0.4 mg/daily. At the age of 3 years, hypertension was detected while his electrolyte levels were normal. His treatment was discontinued. At the eighth day without treatment, aldosterone was 10 pg/mL (50-900 pg/mL), PRA >10 ng/mL/hr (1-6.5 ng/mL/hr), corticosterone 1.5 ng/mL (0-3.5 ng/mL), 18-OH corticosterone 15 ng/dL (6-85 ng/dL), 18-OH corticosterone/aldosterone 15 (2.4-10.5), Na, 132 mmol/L, and K 5 mmol/L.
Genetic sequencing identified that the proband has homozygous p.I236N mutation in CYP11B2 gene and his parents were both heterozygous. Despite this mutation was not reported in any database, another Turkish family was reported with same clinical features recently. PolyPhen-2, SIFT, and MutationTaster indicated this mutation as harmful.
Although there is no functional study of the reported p.I263N mutation which is assumed to be the cause of the disease, we present this case because two independent families were reported with the same clinical features and the mutation was predicted to be harmful by in silico methods.