Non-hepatic hyperammonaemia: an important, potentially reversible cause of encephalopathy

Abstract

The clinical syndrome of encephalopathy is most often encountered in the context of decompensated liver disease and the diagnosis is usually clear cut. Non-hepatic causes of encephalopathy are rarer and tend to present to a wide range of medical specialties with variable and episodic symptoms. Delay can result in the development of potentially life threatening complications, such as seizures and coma.Early recognition is vital. A history of similar episodes or clinical risk factors and early assessment of blood ammonia levels help establish the diagnosis. In addition to adequate supportive care, investigation of the underlying cause of the hyperammonaemia is essential and its reversal, where possible, will often result in complete recovery. Detection of an unborn error of metabolism should lead to the initiation of appropriate maintenance therapy and genetic counselling. (Postgrad Med J 2001;77:717-722)

Noncirrhotic Hyperammonemia Causing Relapsing Altered Mental Status

“…In our patient, the elevated blood ammonia level and the rapid resolution of symptoms coupled with the reduction of his blood ammonia level led us to suspect that hyperammonemia may have accounted for his presentation. His clinical presentation and subsequent clinical course were similar to those of patients described in prior case reports of noncirrhotic/nonhepatic hyperammonemia (2)(3)(4)(5)(6)(7)(8).…”

“…On the other hand, hyperammonemia is also known to be a rare complication of malignancies with and without chemotherapy (4). It has been reported as complicating acute leukemias, multiple myeloma, and solid organ tumors.…”

“…Secondary hyperammonemia occurs commonly in the presence of hepatic disorders leading to portosystemic encephalopathy, but can occur in the absence of hepatic dysfunction in disorders like Reye's syndrome, ureterosigmoidostomy, and infection in a neurogenic bladder. Drug toxicity as a result of disruption of mitochondrial pathways by drugs like cyanide, carbamazepine, valproic acid, iron, and cytotoxics can also cause secondary hyperammonemia, and this is thought to be the main mechanism by which nonhepatic or noncirrhotic hyperammonemia can occur in people exposed to these drugs (2,(4)(5)(6)(7)(8)(9).…”

“…In the case of altered mental status of unknown etiology, the diff erential diagnosis is wide and includes toxic-metabolic, traumatic, functional, vascular, and infectious causes. Th e syndrome of noncirrhotic or nonhepatic hyperammonemia, by which we mean raised blood ammonia levels in the setting of normal liver function, is an increasingly recognized and reported cause of altered mental status (1)(2)(3)(4)(5). Although it is not very common, it is important for clinicians to be aware of this entity, since the timely diagnosis requires a high index of suspicion, particularly in predisposed patients, and the therapeutic outcome is good if well managed.…”

Hyperammonemia in a patient with obstructive urinary tract infection due to Corynebacterium urealyticum

“…However, some nonhepatic causes of hyperammonemia are severe enough to cause confusion and coma. There are numerous possible causes of hyperammonemia: gastrointestinal bleeding; portal circulation shunt; vesicorectal fistula; inherited defects of the urea cycle enzymes; transport defects in the urea cycle intermediates; organic acidurias; other metabolic causes (for example, hyperinsulinemic hypoglycemia, distal renal tubular acidosis); drugs (for example, 5-fluorouracil, asparaginase, sodium valproate, halothane, enflurane); and parenteral nutrition [1].…”