Objectives: Pseudohypoaldosteronism type 1(PHA 1) is a rare hereditary disorder characterized by resistance to the actions of aldosterone. Two different modes of inheritance with different mechanisms and clinical manifestations have been described, Autosomal recessive that affects the epithelial sodium channel (ENaC),the defect is permanent and affects all aldosterone target organs. Autosomal dominant or sporadic PHA 1, affects the mineralocorticoid receptor in most patients.
Methods: Four unrelated Palestinian infants to a consanguineous Palestinian families presented in the first week of life with severe dehydration, hyponatremia, hyperkalemia and severe metabolic acidosis, assessed to have pseudohypoaldosteronism and were managed with hypertonic saline and kayexalate, and did not improve on mineralocorticoids. Plasma renin activity & Aldosterone levels were extremely elevated.
Results: Whole exom sequencing and subunit genes of the ENaC were sequenced and revealed four novel mutations, R73C (Arg73Cys)mutation in the SCNN1A gene in one patient, c.142-143insC mutation that leads to frameshift and premature stop codon(p.S47fsX69) of SCNN1G gene in another patient, c.69delG causing frameshift and stop codon (p.G23GfsX26) of SCNN1A in another patient and G315R (Gly315Arg) in exon 6 of codon 315 of SCNN1B gene.
Conclusions: To our knowledge, this is the first description of this disease in a Palestinian family with molecular confirmation, allowing accurate genetic counseling, early diagnosis of affected kindreds, early therapeutic interventions and avoiding complications and checking if the clinical presentation does correlate well with the specific genotype.
19 - 21 Sep 2019
European Society for Paediatric Endocrinology