Bartter syndrome (BS) as salt-losing tubulopathy is a heterogeneous rare genetic disease occurring due to a deficiency in sodium and chloride reabsorption from urine back into the bloodstream. Bartter syndrome is seen in 1 in 1,000,000 individuals. Patients often present in infancy with failure to thrive. Bartter syndrome is difficult to recognize. Untreated cases are associated with significant morbidity and mortality.

There are several categories for Barter syndrome. In terms of the time of onset of symptoms, it is classified into two groups: classical and prenatal. Based on molecular studies, BS is divided into 5 types: SLC12A1 (600839, type I), KCNJ1 (600359, type II), CLCNKB (602023, type III), BSND (606412, type IVa), CLCNKB and CLCNKA (602024) co-mutated (type IVb), and CASR (601199, type V). Bartter syndrome type IVb is Digenic recessive disorder caused by a combination of disrupting mutations in genes CLCNKA and CLCNKB, encode protein subunits of the voltage-gated chloride channel family. Recent advances in medical genetics through next-generation sequencing (NGS) have resulted in a better understanding of several human inherited diseases.

The current report described a 3-year-old boy from a consanguineous family with BS (type 4b) presenting with restlessness, failure to thrive, hypokalemia, hyponatremia, and metabolic alkalosis. This case showed homozygous novel mutation in CLCNKA (c.944A>T, p.Tyr315Phe) and heterozygous reported mutation in CLCNKB (c.641_642delCAinsGC, p.Ala214Gly). To date, only a few cases of Bartter syndrome representing digenic mutations in two different genes have been reported This case provides apparent evidence of digenic inheritance and this is the first reported case of such mutations and a collection of pathologies in a newborn child.

 

Keywords: Bartter syndrome, CLCNKA gene, CLCNKB gene, Metabolic alkalosis, Chloride channel