ESPE Abstracts

Background: Pseudohypoaldosteronism type 1 (PHA1) is a rare disorder of neonatal salt loss unresponsive to mineralocorticoids, requiring salt supplementation. It results from resistance of kidney and/or other tissues to mineralocorticoids, arising from mutations in genes encoding mineralocorticoid receptor (MR: NR3C2; autosomal dominant), or epithelial sodium channel (ENaC) genes (SCNN1A/B/G; autosomal recessive). Milder clinical phenotype associates with renal PHA1 (NR3C2) and shows variable penetrance. PHA1 may be distinguished from PHA2 (2ary to urinary tract abnormalities) by urinary steroid profiling (USP).

Objectives, hypotheses and methods: Case reports: two families/three patients.

Results: Pt 1: female, BWt 3.1 kg, 1st child non-consanguinous Caucasian parents. Presented at 3 weeks below BWt with Na 125 mmol/l; K 6.5 mmol/l; glucose, cortisol post-Synacthen, blood gas: Normal. USP diagnostic of PHA1; Aldo 36 000 (n<2000) pmol/l, PRA 61 (n<3 pmol/ml per h). Stabilised with oral NaCl supps after IV saline treatment. Subsequently thriving, now age 2 years on ~1 mmol/kg per day oral NaCl. Diagnosis presumed NR3C2 clinically. Neither parent has relevant childhood history. Pt 2: male, newborn sib. Pt 1. BWt 4.1 kg, 39 weeks, Feb/2014 – prospectively evaluated for possible PHA1, even though parental history negative. Day1&2 U/Es and USP normal. Day7 U/Es Na 136/K 5.3 mmol/l; USP diagnostic of PHA1. Day15: Wt loss to 3.88 kg, NA 139/K 4.2 mmol/l started NaCl supps 5 mmol/l per kg per day; Aldo 3670 pmol/l (n<800)/PRA 282 mU/l (n<60). Clinically well since. Pt 3: female, born 36 weeks, Romanian/Indian parents. EmLSCS for PROM. Admitted with 7% wt loss at 12 days; Na 132/K 6.3 mmol/l. Considered PHA2 (no maternal infection proven)/congenital adrenal hyperplasia (but no virilising signs). Cortisol response to Synacthen, renal USS and MSU normal. Antibiotic treatment and improved feeding. U/Es normalised. Patient discharged by General Team at 1 week pending endocrine (Aldo/PRA) results. Readmitted recurrent salt-wasting crisis/collapse. Initial USP consistent with PHA1 or PHA2 – Subsequent definitive USP supports diagnosis PHA1. Genetic analysis is in process with both families.

Conclusion: USP analysis is a critical and essential component for diagnosis of salt-wasting disorders in neonates.