Persistent Flaccid Paralysis in a Patient with Bartter Syndrome

Case report

A two-year-old girl with an unremarkable family history was transferred to our tertiary care centre showcasing a severe dyselectrolytemia and a suspicion of tubulopathy. She was born to healthy nonconsanguienous parents at 35 weeks of gestation from dizygotic twins with birth weight of 2,550 g, polyhydramnios was not reported. One week prior to her admission to our department, she exhibited symptoms of acute upper respiratory tract infection and was admitted to the local hospital. Her physical examination showed mild dehydration, general muscle weakness, significantly reduced spontaneous physical activity and feeding difficulties initially attributed to an electrolyte imbalance. Laboratory examination revealed severe hypokalemia (2.1 mmol/L), hypernatremia (154.9 mmol/L), hypochloremia (91.0 mmol/L) and metabolic alkalosis (pH 7.6, bicarbonate 31.0 mmol/L). Both plasmatic renin and aldosterone were high: 643.5 ng/L and 5.9 nmol/L, respectively.

She was rehydrated by an isotonic intravenous solution with high concentration of potassium. This therapy resulted in mild improvement of her hydration, physical activity and an adequate urine output (2 mL/kg/h). Ultrasound then revealed normal kidneys bilaterally without any nephrocalcinosis. Our patient required high potassium replacement to maintain normal serum values (7.5 mmol/kg/day of KCl). Potassium serum levels increased to normal range (4.0 mmol/L), chloride (99.0 mmol/L) and sodium (135.0 mmol/L) were borderline, however her muscle weakness persisted. The brain and kidney computed tomography was performed with normal findings. Cerebrospinal fluid (CSF) analysis revealed normal cell count with borderline protein levels of 460 mg/L (normal value 150–450). Nerve conduction studies were normal but neuropathy appeared suspicious. At this point, the paediatric patient was transferred to our department for further diagnostics and care.

Upon admission, the patient was well hydrated with prescribed potassium oral and parenteral substitution. Laboratory results showed mildly decreased magnesium of 0.75 mmol/L, borderline sodium 135.0 mmol/L, chloride 99.0 mmol/L, normal kalemia of 3.9 mmol/L with high potassium transtubular gradient (20), fraction excretion of sodium 0.37%, potassium 32.7% and chloride 15.0%. Therefore, cyclooxygenase inhibitor therapy (celecoxib 5 mg/kg/day in two doses) was administered along with the continuing KCl substitution.

Despite the patient’s normalised laboratory findings, the physical examination deteriorated. Neurologists described flaccid quadriparesis and bulbar syndrome. Subsequently, a second lumbar puncture was performed. The CSF analysis revealed further progression of protein elevation (CSF protein 579 mg/L), blood-brain barrier failure, yet cell count remained normal. Magnetic resonance imaging (MRI) of the spine revealed gadolinium enhancement of nerve roots ([Fig. 1]). Nerve conduction studies showcased signs of mild motor-sensitive demyelinating polyneuropathy. In addition, anti-sulfatide immunoglobulin M (IgM) and IgG along with myelin-associated glycoprotein (MAG) antibodies were identified in the patient's serum. Based on these findings the Guillain-Barré syndrome (GBS) was diagnosed. Intravenous high-dose immunoglobulin (IVIG) therapy was commenced (0.4 g/kg for five consecutive days) and complemented by intensive complex physiotherapy at the department of paediatric neurology. The patient's neurological condition began to improve significantly immediately after the IVIG administration with almost complete restoration in motor functions within six weeks. Patient’s serum potassium remained in normal range.

Fig. 1 a) Sagittal T2WI magnetic resonance (MR) in a Guillain-Barré syndrome patient reveals thickened cauda equina. The conus has a normal morphology and exhibits normal signal intensities. Sagittal b) and axial c) T1WIC+ MR demonstrate smooth linear cauda equina thickening and vivid contrast enhancement.

Molecular genetic analysis revealed a pathogenic heterozygous deletion of the entire CLCNKB gene as well as a pathogenic missense variant in the CLCNKB gene (c.908 A>G, p.Gln303Pro). The combination of these two variants in the CLCNKB gene has been described as causative Bartter syndrome (BS).

Publication History

Article published online:
27 February 2023