ESPE Abstracts

Aldosterone synthase deficiency (ASD) is a rare cause of hyponatremia, commonly found in infancy and if diagnosed early it has a good prognosis. ASD has been classified into 2 types, type 1, which is the rarest form, and type 2. Patients with ASD usually present with salt-wasting, insufficient release of potassium in the urine and failure to thrive in early infancy. This paper reports on one ASD case of a 6-week-old female who presented with a salt-wasting crisis, hyperkalemia and failure to thrive. During the initial ICU admission phase, ASD was not suspected due to nonspecific signs. During the second admission to the ICU, two weeks after the initial admission, laboratory investigations were repeated and electrolyte test revealed hyponatremia (128 mmol/l), hyperkalemia (6.50 mmol/l) and hypercalcemia (1.48 mmol/l), 17-hydroxyprogesterone was in the normal range (1.27 ng/ml), excluding the majority of congenital adrenal hyperplasia forms. During hospitalization, sequential blood gas analyses were collected revealing persistent hyponatremia and hyperkalemia. Additional tests for the hypothalamic-pituitary-adrenal axis - cortisol and ACTH were in the normal range, excluding primary adrenal insufficiency, aldosterone level had inappropriately normal value (14.9 ng/dl) and renin value was above the detection limit (> 5000 uUI/ml), the fasting blood glucose was in the normal range (84 mg/dl), plasmatic osmolality was 259.11 mOsm/kg and the urine osmolality was inappropriately high (207.38 mOsm/kg). The endocrinologist requested pediatric nephrology evaluation and genetic counselling (searching for causes of aldosterone synthase (CYP11B2) deficiency/aldosterone resistance) and started empiric fludrocortisone therapy. Genetic testing was considered and WES testing identified two heterozygous pathogenic and likely pathogenic variants in the CYP11B2 gene, which confirmed ASD. The infant was reevaluated at 3 months old and the laboratory tests found that cortisol and electrolyte test had normal values and the renin value dropped at 648.2 uUI/ml, so it was possible to calculate the aldosterone-to-renin ratio, which was low (0.009), suggestive for primary hypoaldosteronism. The endocrinologist also requested the 18-hydroxycorticosterone value, which was normal, suggestive for ASD type 1. In our patient, treatment with oral sodium supplementation and fludrocortisone was initiated in October 2023, with progressive increasing doses and the infant rapidly started to catch up growth. Through this case report, we aimto underline the importance of early recognition of this life-threatening pathology through hormonal investigations, followed by genetic testing, to facilitate the clinical management of the patient.