ESPE Abstracts

Introduction: Aldosterone synthase deficiency (ASD), also known as Corticosterone methyloxidase deficiency, is a rare autosomal recessive disorder characterized by severe hyperkalemia, salt loss, vomiting, severe dehydration and failure to thrive. It is caused by inactivating mutations of the CYP11B2 gene. We herein report the first confirmed Egyptian infant who had clinical and hormonal features of aldosterone synthase deficiency. Unexpectedly, our patient had hypertension at diagnosis.

Case summary: A 4-month-old boy born to consanguineous parents with a birth weight of 3.700 Kg, presented with faltering growth noticed since the age of 2 months. He had history of recurrent vomiting and poor feeding, and no history of polyuria or polydipsia. His weight was 4.5 KG (-3SD), length 51 cm (-4.3SD), penile length 3 cm, and palpable testes. Despite being dehydrated, his blood pressure was between the 95th and 97th percentiles for age. His laboratory investigations showed hyponatremia, hyperkalemia, and metabolic acidosis. His random blood sugar, and renal functions were normal. Congenital adrenal hyperplasia was excluded with normal levels of 17-hydroxyprogesterone 1.04 ng/ml (0.34-4.7), ACTH 8am 4.32 pg/ml (7.2-63), and cortisol 8 am 20.97 mg/dl. Pseudohypoaldosteronism was suspected due to the elevated blood pressure, however, renin, aldosterone were done showing hyperreninemic hypoaldosteronism. He had elevated spot Na 58 mEq/L, and Cl 30 mEq/L in urine, with low urine K 6.2 mEq/L and a transtubular potassium gradient of 2. Ultrasonography of the kidneys and adrenal glands were normal. These findings suggested a diagnosis of aldosterone synthase deficiency, and treatment with fludrocortisone, sodium chloride 3%, and oral bicarbonate was started. In addition, therapy with angiotensin-converting enzyme inhibitor was transiently required initially to control elevated blood pressure. A novel homozygous pathogenic variant was identified by genetic analysis in CYP11B2 (c.1012C>T, p.Gln338Ter) confirming the diagnosis of congenital hypoaldosteronism due to corticosterone methyloxidase II deficiency.

Conclusion: Although a rare cause of hyperreninemic hypoaldosteronism, aldosterone synthase deficiency should be suspected in infants presenting with salt-wasting. It is a life-threatening disease, if left untreated; however, it has a good prognosis when adequate fludrocortisone replacement is given. Hypertension has been rarely reported and is postulated to be caused by the high levels of renin and angiotensin II as potent vasoconstrictors.