K, a morphologically normal female baby was born at term to unrelated parents, and presented at six days of age with life threatening shock (Lactate 7.8mmol/L), hyperkalaemia (11.5mmol/L) with runs of VT, and hyponatraemia (120mM).  Spot urine showed urine Na 95 mmol/L and Urine K 3 mmol/L despite hyponatraemia.  Urine metabolic profile, renal ultrasound and echocardiogram were normal. The working diagnosis was isolated defect in mineralocorticoid biosynthesis or pseudohypoaldosteronism type 1.

Subsequent investigations revealed a Cortisol of 1407 nmol/L, renin (1253 mIU/L) and aldosterone (>30,000 & 47,000 pmol/L).                

Her adopted father had been on an ACEI for hypertension since 19 years of age.

Initial treatment included normal saline boluses, bicarbonate infusion, calcium gluconate and insulin-dextrose infusions and resonium for hyperkalemia and shock which resulted in normalisation of her fluid volume and electrolytes.  IV antibiotics were used until sepsis was excluded - blood cultures were sterile.  High dose fludrocortisone was trialled for several days without effect.  K was commenced on normal saline infusion for slow correction of her sodium deficit.  She was subsequently commenced on oral sodium chloride (20%), sodium bicarbonate and a low potassium and high sodium formula and was discharged home at 4 weeks age. 

Molecular confirmation of a diagnosis of recessive PHA1 was received, demonstrating compound heterozygous mutations in the SCNN1A gene.  K is now 18 months old and is tracking well in her growth and development (Weight 10th centile; height 25th centile), although has had recent weight loss, vomiting and delayed gastric emptying.  She is on a low potassium formula and salt replacement via PEG feeds as she has food aversion which is being managed.  She is currently doing well with a total Na replacement of 11mmol/kg/day (2/3 as Na citrate and 1/3 as NaCl).  She is on regular resonium 0.3mg bd guided by potassium levels, domperidone 2mg bd, erythromycin 20mg bd and ferroliquid 3ml daily.  She has had a chronic cough since age 1 month which improved with macrolides and prokinetic agents as well as gastrojejunal feeds indicating gastroesophageal reflux may be contributing.  Her CT chest showed bronchial wall thickening and mucus impaction in the posterior segment of the right upper lobe with patchy consolidation.         

Pseudohypoaldosteronism type 1 is a rare genetic disorder caused by mutations in one of the 3 subunits of the the amiloride-sensitive sodium channel - ENaC (1)(2).  ENaC is decreased in autosomal recessive pseudohypoaldosteronism type1, resulting in aldosterone resistance in multiple organs.  In contrast, autosomal dominant PHA1 is due to loss of function mutations of the NR3C2 gene which encodes for the mineralocorticoid receptor, (1)(3) and this may be isolated to the kidney which generally results in a milder phenotype that often improves with time. 

Issues:

1)      Management of growth with vomiting, delayed gastric emptying, food aversion

2)      Risk of future chest infections

3)      Planning for future pregnancies, genetic counselling

4)      Further investigation of hypertension with father with hypertension from age 19, paternal grandmother with hypertension and now older sibling with hypertension

5)      Role of carbenoxolone therapy