Severe non-hepatic hyperammonaemic encephalopathy in an immunocompromised adolescent with enterocolitis

Abstract

Non-hepatic causes of hyperammonaemia are uncommon relative to hepatic aetiologies. An adolescent female was admitted to the hospital with a diagnosis of very severe aplastic anaemia. During her treatment with immunosuppressive therapy, she developed neutropenic enterocolitis, pseudomonal bacteraemia and hyperammonaemia. A combination of intermittent haemodialysis and high-volume continuous veno-venous haemodiafiltration (CVVHDF) was required to manage the hyperammonaemia. Despite a thorough investigation, there were no hepatic, metabolic or genetic aetiologies identified that explained the hyperammonaemia. The hyperammonaemia resolved only after the surgical resection of her inflamed colon, following which she was successfully weaned off from the renal support. This is a novel case report of hyperammonaemia of non-hepatic origin secondary to widespread inflammation of the colon requiring surgical resection in an immunocompromised patient. This case also highlights the role of high-volume CVVHDF in augmenting haemodialysis in the management of severe refractory hyperammonaemia.

Keywords: Haematology (drugs and medicines); Haematology (incl blood transfusion); Hepatitis other; Infection (gastroenterology); Paediatric intensive care.

Figure 1

Ammonia level (µmol/L) indicated by black dots. Cumulative CVVHDF over 24 hours (ml/kg/hour) is shown by red triangles. A normal ammonia level of less than 50 µmol/L is indicated in blue/shaded area. AKI, acute kidney injury, CVVHDF, continuous veno-venous haemodiafiltration; HD, haemodialysis; PICU, paediatric intensive care unit.

Figure 2

A schematic representation of the sources of ammonia production and its excretory pathway. Ammonia is primarily generated by the small intestine, metabolised in the liver into urea and subsequently excreted in urine as urea and ammonium. The liver’s urea cycle pathway becomes the most vital process to eliminate ammonia. The ammonia level can become high if there is a problem in liver, urea cycle pathway or if they both are normal but are overwhelmed by increased production. In our case, we propose a pathological additional source of ammonia in the colon via urease-producing bacteria and increased absorption of ammonia through the necrosed bowel.