Endocrine Abstracts

We would like to present the case of a twenty-six year old gentleman whose first presentation to hospital was aged 4 days old. At that time he was thought to be generally unwell with poor feeding and excessively somnolent. During his resuscitation he was found to have extremely deranged serum electrolytes with sodium 122 mmol/l and potassium 14 mmol/l. His electrocardiogram (ECG) was initially noted to be bizarre, with no clear rhythm. After resuscitation with IV fluid, glucose and insulin his potassium improved to 10 mmol/l and the ECG reverted back to sinus rhythm. Further investigations following his stabilisation showed that he had excessively high aldosterone and renin levels with a biochemical picture more in keeping with hypoaldosteronism. On this basis a presumed diagnosis of pseudohypoaldosteronism was made. It took a number of weeks to ascertain the daily sodium requirement given his very high urinary and sweat sodium concentrations. Once stable he was converted to a regime of oral slow sodium and calcium resonium, both at high doses: slow sodium 16 tablets per day and resonium 16 g daily. He has 3 younger siblings the elder two of which are unaffected. His youngest brother was noted by his mother to have excessively salty sweat and has gone on to have the same clinical diagnosis, although less severe in phenotype. There is no evidence to consanguinity. He has maintained a nearly normal life on the basis of intermittent additional dosing of calcium resonium and sodium when his potassium levels rose. Additionally he once needed hospital treatment during excessively hot weather and he became hyponatraemic due to profuse sweating. He has never had recurrent lung infections or skin disorders as a results of high sweat sodium content. In adult life he underwent screening for genetic causes of his condition and was found to have a homozygous mutation in the amiloride sensitive sodium channel subunit alpha. The c.1339dup pathogenic variant is predicted to case a frameshift mutation and premature truncation p.(Tyr447leufs*13). This is a mutation known to cause pseudohypoaldosteronism type 1. The disorder is estimated to affect 1 in 80,000 children and can be inherited in an autosomal dominant or recessive fashion depending on the gene affected. We aim to undertake further genetic testing in members of his family and continue genetic counselling. He continues to need careful management of electrolytes during intercurrent illness.