Congenital chloride diarrhea (DIAR1) is a rare autosomal recessive disorder associated with the inability of the intestine to properly absorb electrolytes, particularly chloride, causing dehydration and metabolic acidosis. DIAR1 can manifest prenatally and the clinical features include abdominal distension, visible peristalsis, polyhydramnios, reduced blood electrolytes, increased blood bilirubin levels, failure to thrive, lack of meconium in newborns, premature birth, watery diarrhea, hyperaldosteronism, hypokalemia, hyponatremia, high chloride levels in stool and high rennin levels in the blood.
Congenital chloride diarrhea (DIAR1) is linked to mutations in the SLC26A3 (solute carrier family 26, member 3) gene located on chromosome 7.
Lubani et al. (1989) reported 16 Kuwaiti children with congenital chloride diarrhea (CCD) throughout a period of seven years (1980-1986) and calculated its incidence at approximately 7.6/100,000 live births. The cohort comprised of nine boys and seven girls with a mean age of three years and 10 months. All mothers were found to be positive for a history of hydramnios throughout pregnancy, three mothers underwent sonography, and all patients were delivered through preterm delivery with a birth weight of less than 2500g. Eleven children were confirmed clinically and biochemically to have jaundice, while out of 16 children, six were siblings and eight were found to experience siblings' death due to severe dehydration secondary to diarrhea. CCD diagnosis was confirmed through stool electrolytes which presented high fecal chloride (FCL) concentration that exceeded the sum of fecal sodium and potassium. All subjects underwent adequate replacement therapy which resulted in 15 children surviving and one patient passing away due to renal failure. To the finest knowledge of Lubani et al. (1989), their report was considered to be the first in an Arab country and the largest series described from a single country following Finland.
Abdullah et al. (1990) reported a Saudi boy who was antenatally suspected of having congenital chloride diarrhoea (CCD) with the diagnosis being confirmed post-natally and successfully managed.
Kaglawalla (1994) retrospectively reviewed the medical records of all children admitted to a single 550 bed hospital in Riyadh between 1976 and 1993 with a diagnosis of CCD. Of the 32,623 live births recorded in this study period, 10 children (seven boys, three girls; mean age: 10 months) with CCD were identified, indicating a fairly common occurrence of the condition in the country. Eight of these 10 children had consanguineous parents. Two patients were siblings, and their cousin was also affected. In all cases, the mothers had histories of polyhydramnios. Nine patients had abdominal distensions and jaundice at birth. Biochemical examination revealed hypokalemic hypochloremic metabolic acidosis in five patients. All patients had fecal chloride levels greater than 100 mmol/L. All the patients were growth retarded at the time of diagnosis. The patients were treated with isotonic intravenous fluids followed by oral replacement solutions of NaCl and KCl. Only six patients were followed for over two years. Of these six patients, five complied with the continuous oral replacement therapy. Four of these five achieved significant catch up growth, and were developmentally normal, although their weights were still below normal for their age. One child with neonatal intraventicular hemorrhage and a poorly compliant patient were both growth retarded and mentally subnormal.
Wani et al. (2009) described the first association of congenital chloride diarrhea with congenital cataract. The neonate was born at 36 weeks gestation to consanguineous parents. At 33 weeks gestation, US had revealed polyhydramnios and dilated bowel loops in the fetus that were further confirmed by X-ray. At birth, the baby was passing watery stools and no meconium. The abdomen was distended with visible gut loops. Laboratory analysis revealed serum chloride of 109 meq/l. Arterial blood gas analysis revealed metabolic acidosis. A diagnosis of chloride loosing diarrhea was made, and the neonate was started on sodium and potassium replacement. The baby tolerated oral feeds, started passing meconium after 20 days, and, subsequently, had normal growth. The baby was also found to have congenital cataract, which was operated on 4-weeks later.