Congenital Chloride Diarrhea in Dizygotic Twins
A 6-month-old male presented to our outpatient clinic with poor feeding and irritability. He was the second of non-identical twins, born by cesarean section at 32 and 2/7 weeks gestational age due to preterm labor and transverse lie of one fetus. Since their mother had polyhydramnios and both showed small bowel dilatation on prenatal ultrasound (), both newborns were suspected to have congenital intestinal obstruction and their mother was transferred to this hospital before delivery. Amnioreduction has been conducted twice at previous hospital but there were no data for diagnosis such as amniotic fluid analysis. The birth weight of the male twin was 2,130 g and that of the female was 1,720 g. They were treated in the neonatal intensive care unit (NICU) for prematurity and low birth weight. During that time, they showed recurrent abdominal distension and ileus, but there was no evidence of bowel obstruction on either abdominal sonography or small bowel series (). They were discharged at 42 day of age.\nOne month later, the male was admitted for poor weight gain. Sucking was insufficient and he was irritable. He had hyponatremia and metabolic alkalosis. Blood gas analysis showed a pH of 7.645 and a base excess of +16.0 mmol/L. Other laboratory findings were serum sodium 115 mEq/L, serum potassium 2.6 mEq/L, serum chloride 57 mEq/L. urine sodium 8 mEq/L, urine potassium 3.2 mEq/L, urine chloride 9 mEq/L, urine osmolality 61 mOsm/kg H2O, and serum osmolality 235 mOsm/kg H2O. Renin activity (116.89 ng/mL/h; normal range, 2.0-35.0 ng/mL/h) and aldosterone level (>1,393 pg/mL; normal range, 65-860 pg/mL) were elevated. He had watery diarrhea, but stool culture and stool occult blood examinations were negative. Electrolytes were corrected and symptoms improved. He was discharged but the cause of hyponatremia and metabolic alkalosis was not clear.\nThe infant was admitted at 6 months of age because of diminishing body weight and developmental delay. He was only able to consume milk and could not eat solid food. He was unable to lift his head or roll over, did not grasp anything and rarely laughed or babbled. His body weight was 3.6 kg (corrected age, 4 months; below the 3rd percentile) and his height was 60 cm (corrected age, 4 months; 5th to 10th percentile). He again had hyponatremia and metabolic alkalosis. Urine osmolality was elevated and urine sodium was low: urine sodium <10 mEq/L, urine potassium 8.9 mEq/L, urine chloride 8 mEq/L, urine osmolality 390 mOsm/kg H2O and serum osmolality 215 mOsm/kg H2O. Hypotonic hyponatremia with urine osmolality >100 mOsm/kg, decreased extracellular fluid volume, and urine sodium <10 mEq/L suggest presence of extrarenal solute loss. Metabolic alkalosis with low urine chloride (<10 mEq/L) suggest vomiting, gastric drainage, diuretic use, or chloride-losing diarrhea, and other common misdiagnosis such as Bartter's syndrome could be excluded. This results prompted evaluation of fecal electrolytes. He had been experiencing numerous daily episodes of watery stool. Stool Cl- and pH was 124 mEq/L and 6.18, respectively. He was diagnosed as CLD ().\nThe patient had been born to non-consanguineous parents. His twin sister was doing well after discharge from NICU but she also had frequent diarrhea and growth retardation (corrected age, 4 months; body weight 5.1 kg, below the 3 percentile) and her twin brother was diagnosed with CLD. She was also underwent some blood tests with exams on stool electrolyte, confirming her with CLD as well. She showed relatively minor abnormality in electrolyte level of serum and stool than her twin brother ().\nAt the present time, 13 months after diagnosis, both twins are orally receiving NaCl and KCl. The dose of NaCl and KCl dosage were adjusted with constant monitoring of the patients' electrolyte level. In the last outpatient clinic, the dosage was NaCl 4.2 mEq/kg/day, KCl 0.8 mEq/kg/day for the male, and NaCl 3.2 mEq/kg/day, KCl 1.2 mEq/kg/day for the female patient. The male's body weight is 10.5 kg (corrected age, 17 mo; 25th to 50th percentile), serum sodium is 141 mEq/L, serum potassium is 4.3 mEq/L and serum chloride is 105 mEq/L. The female's body weight is 10.2 kg (corrected age, 17 months; 25th to 50th percentile), serum sodium is 141 mEq/L, serum potassium is 3.7 mEq/L and serum chloride is 103 mEq/L. Their serum electrolytes are being maintained within normal range and their body weights and developments are gradually improving (). Gene study was recommended, but parental consent was not given.