Prvé prípady geneticky potvrdenej kongenitálnej hnačky so stratou chloridov na Slovensku

Abstract

Chloride ions are involved in regulating cell volume, secreting body fluids and maintaining acid-base balance. Hypo/hyperchloraemia in neonates and infants is an emergent situation requiring careful differential diagnosis to detect a cause of the condition. The rare causes of severe hypochloremia include congenital chloridorhea (CLD), characterized by profound bulky diarrhea, high chloride concentration in stool, and severe metabolic alkalosis. CLD is a rare autosomal recessive disease caused by the mutation of the SLC26A3 gene located on chromosome 7q31, which encodes the transmembrane protein in intestinal cells. Genetic defect causes a disorder of intestinal chloride absorption and bicarbonate secretion. Profound diarrhea induces significant losses of water and electrolytes, leading to volume depletion, hyperreninemia, hyperaldosteronism, renal loss of potassium and occasionally to the development of chronic nephropathy. The authors present rare cases of two brothers with genetically confirmed CLD. Both children were born with lower birth weight and shortly after birth required administration to ICU because of notable distended abdomen and diarrhea with severe dehydration and electrolyte imbalance. Significant hypochloraemia (76 mmol/l or 78 mmol/l) and extreme metabolic alkalosis (pH 7.63; HCO3 46 mmol/l and pH 7.73; HCO3 40 mmol/l resp.) were dominant laboratory features. Renal chloride losses and cystic fibrosis were excluded; the chloride concentration test in stool was not available. After intravenous suplementation of electrolytes, the biochemical abnormalities were partially normalized and watery stools persist. In further development, the frequent episodes of dehydratation reguiring the parenteral treatment were present. Renal functions are at age 6 or 2 years resp. normal, but USG signs of nephrocalcinosis in the older boy have been observed. By molecular genetic testing the same genotype in both siblings was identified the previously not described variant c.629_63Ildel (p.Ile210del) and the pathogenic variant in the heterozygous state of the SLC26A3 gene. In persistent watery diarrhea, hypochloraemia, hypokalaemia and metabolic alkalosis, a congenital chloridorhea should be consider. The diagnosis is based on a typical clinical picture of watery diarrhea from neonatal age, evidence of a high chloride concentration in stool > 90 mmol/l and molecular-genetic examination. CLD patients require regular nephrologic monitoring for the risk of chronic nephropathy or functional tubular damage.