DEFECTIVE JEJUNAL BRUSH BORDER Na+|[sol]|H+ EXCHANGE IN LETHAL FAMILIAN PROTRACTED DIARRHOEA

The clinical spectrum of disease associated with the recently described defect in jejunal brush border membrane (BBM) Na+/H+ exchange remains poorly defined. We describe a further, lethal case of protracted diarrhoea in a child from a family in whom 2 previous siblings died of protracted diarrhoea at 2 and 11 months. The patient, a boy, was born at term weighing 2.9 kg and was admitted at 6d with profuse watery diarrhoea, severe dehydration and metabolic acidosis. Parenteral nutrition was started but the diarrhoea persisted, and he developed severe necrotising enterocolitis requiring an ileostomy. A high-output secretory diarrhoea persisted during nil by mouth (ileostomy fluid mmol/l: Na+ 128; K+ 10; Cl 96) and reanastomosis. Parenteral Na+ requirement was high (6-10 mmol/kg/d). Extensive investigation of gastrointestinal function was non-contributory, but transport studies on a jejunal biopsy at 3 mo, which showed a mild partial villous atrophy but normal electron microscopy, confirmed a specific defect in Na+/H+ exchange. 15 sec Na+-stimulated glucose uptake by jejunal BBM vesicles was normal (patient: 107 pmol/mg protein; control mean: 213 (SD 111), whereas 15 sec Na+ uptake under H+ - gradient conditions was negligible (patient: 9 pmol/mg protein; control mean: 150 (SD 48)); Na+ uptakes at equilibrium (120 min) were normal. The patient died of severe intercurrent infection at 18 mo. These data therefore extend the spectrum of disorders characterised by a specific defect in Na+/H+ exchange.