Endocrine Abstracts

JOINT3517

Background: Pseudohypoaldosteronism type 1 (PHA1) is a rare, primary form of mineralocorticoid resistance. Infants typically present in the neonatal period with salt wasting, failure to thrive, dehydration and the biochemical findings of hyperkalaemia, metabolic acidosis and elevated plasma aldosterone and renin levels.

Case presentation: We report the case of an 18 day old male infant born to non-consanguineous parents at term with a birth weight of 3.68kg. He presented with poor feeding, lethargy and 11% weight loss. Biochemical investigations revealed severe hyponatraemia (118mmol/L) and hyperkalaemia (9.2mmol/L). He was normoglycaemic (4.3mmol/L) and had a normal pH (pH 7.37). He was initially treated for suspected congenital adrenal hyperplasia with intravenous fluids, stress dose intravenous hydrocortisone and treatment of hyperkalaemia. Broad spectrum antibiotics were commenced for suspected sepsis. His CRP was elevated at 223mg/L and his urine and blood cultures grew E. coli. He was treated with IV antibiotics for 14 days. His cerebrospinal fluid culture was negative. He was switched to oral hydrocortisone, fludrocortisone and sodium supplements and his electrolytes normalised within 24 hours (Na 135mmol/L and potassium 5.9mmol/L). His cortisol returned at 2219 nmol/L. His 17-hydroxyprogesterone (17OHP) also returned normal at 1.9 nmol/L (<20 nmol/L), ruling out a diagnosis of congenital adrenal hyperplasia. His medications were discontinued by day of life 30 as transient pseudohypoaldosteronism was suspected secondary to urosepsis. On weaning of these medications, his sodium dropped to 129mmol/L and his potassium rose to 6.2mmol/L, therefore treatment was restarted pending the results of further investigations. He had a significantly elevated aldosterone >3656 pmol/L (102–670) and a raised direct renin 199.7mIU/L (9.0–103.5). As he required ongoing sodium supplementation despite resolution of his urosepsis, genetic testing was performed. He was successfully weaned off sodium supplements at 6 months of age and is currently 3 years of age with normal electrolytes off treatment.

Results: Genetics testing revealed that he was heterozygous for a pathogenic variant in gene NR3C2 (varint c.2145dupA; p.Glu716Argfs*28) causative for pseudohypoaldosteronism type 1 due to defects in the mineralocorticoid receptor. This variant has not been described in scientific literature prior to this. Parental genetics were carried out and this infant’s mum was also positive for the above mutation.

Discussion: This case describes a rare novel genetic mutation causing pseudohypoaldosteronism in our patient. The main differential for this presentation is transient pseudohypoaldosteronism secondary to urinary tract malformation or urinary tract infection. This patients electrolyte abnormalities persisted despite treatment of his urosepsis prompting genetic testing.