A novel homozygous CLCNKB variant: An early presentation of classic Bartter syndrome in a neonate
Authors: Yaprak Deniz , Kara Hüdaverdi , Calisici Erhan , Karagöl Belma Saygılı , Altan Mustafa 
Published: August 2023

AbstractBackgroundBartter syndrome (BS) is a rare congenital salt‐losing renal tubular transport disorder, characterized by salt wasting, polyuria, biochemical abnormalities, and acid–base homeostasis imbalance. The syndrome has five different genetic forms, and novel mutations of CLCNKB gene lead to type 3 BS also known as classic BS. In this case, we report clinical and molecular findings from a newborn baby with BS.CaseA 10‐day‐old male infant born at 37 weeks of gestation by cesarean section following a pregnancy complicated with polyhydramnios, and fetal distress to a 30‐year‐old gravida 3, para 3 mother, with a 2500 g birth weight was brought to the pediatric emergency department due to weight loss and jaundice. The neonate was referred to the neonatal intensive care unit (NICU) with a preliminary diagnosis of hyponatremic dehydration (Na: 122 mmol/L, 10% dehydration) and hypokalemic hypochloremic metabolic alkalosis (K: 2.13 mmol/L, Cl: 63 mmol/L, pH: 7.62, pCO2: 39 mmHg, HCO3: 40.8 mmol/L, BE: 16.9 mmol/L), and hypocalcemia (ionized Ca: 0.72 mmol/L). On arrival to the NICU, symptomatic focal seizures, and polyuria complicated his course. Spot urine biochemistry revealed a renal salt wasting and hypercalciuria: Creatine 11.4 mg/dL Na: 51 mmol/L (54–150), K: 26 mmol/L (20–80), Cl: 164 mmol/L, fractional excretion of sodium (FENa): 3% (0.9–1.6), fractional excretion of chloride (FECl): 17% (<0.5%) and Ca/Cr: 0.33 (<0.2). Biochemical abnormalities disappeared through intravenous fluid and electrolyte therapy, but he could not achieve adequate weight gain, and polyuric urine output (6.5 cc/kg/h), and metabolic alkalosis continued as the enteral feedings advance. Patient's serum renin: 184 pg/mL (5–27 pg/mL) and aldosterone: 1670 pg/mL (1–180 ng/dL) were elevated. Polyuria, renal salt wasting, electrolyte and acid–base disturbances, and hyperreninemic hyperaldosteronism established the diagnosis as Bartter syndrome. An oral indomethacin (1 mg/kg/day) treatment, on the 8th day. ensured the weight gain, and normalized daily urine output. He achieved the goal of birth weight on the 30th day and he was 3520 g weight at discharge on day 42. The genetic tests of the patient as KCNJ1 SLC12A1 gene sequence analysis revealed a novel homozygous mutation in the 14th exon of the CLCNKB gene, the c.1334_1338del CTTTT (p. Ser445fs*4) variant was identified.DiscussionThe diagnosis of BS should be considered in the presence of a medical history of severe polyhydramnios of fetal origin. Postnatally, polyuria, signs of dehydration, renal salt wasting, and hypokalemic‐metabolic alkalosis should prompt the clinician to request genetic testing for BS in the neonatal period. This case is presented to emphasize that early diagnosis of BS should be considered in newborns presenting with electrolyte abnormalities and metabolic alkalosis accompanying dehydration and favorable growth results can be achieved by starting indomethacin treatment in the early neonatal period. The clinical exome sequencing illustrated a novel missense variant in the CLCNKB gene leading to the molecular diagnosis of BS type 3.