Review
Adult Nonhepatic Hyperammonemia: A Case Report and Differential Diagnosis

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Abstract

This article presents a case report of nonhepatic hyperammonemia, i.e., elevated serum ammonia secondary to a nonhepatic etiology. It then discusses the importance of broadening one's differential diagnosis to include such nonhepatic causes of elevated ammonia levels, and provides a short review of rarer causes of hyperammonemia in the adult population. Treating the underlying condition is the best way to prevent recurrence of hyperammonemia. However, symptomatic treatment should not be delayed while investigating the underlying source.

Section snippets

Case Report

Our patient—Mr. N—was a pleasant 63-year-old gentleman who had incurred a left occipital lobe intracranial hemorrhage with residual right hemianopsia, alexia, and apraxia 4 months before his presentation at our medical center. It was because of this hemorrhage of unclear etiology, continued headache, and seizure prophylaxis that his hometown neurologist prescribed levetiracetam (Keppra [UCB Inc., Smyrna, GA]) and valproic acid (Depakote [Abbott Laboratories, Abbott Park, IL], divalproex,

Differential Diagnosis

In a patient with hyperammonemia, hepatic etiology is often at the top of a differential diagnosis list. However, as in the case of our patient, if hepatic function is normal or at baseline, then other causes of hyperammonemia must be sought. Other explanations for nonhepatic hyperammonemia in the adult patient include medication effects, urinary tract infections, late-onset enzymatic deficiencies, and other miscellaneous causes. With some basic information, the astute clinician can begin to

The Urea Cycle—Excretion of Ammonia

Amino acids in the body are acquired from the diet, created anew, or formed secondary to protein degradation. Amino acids in excess of the body's needs are catabolized via biochemical transamination and deamination, resulting in ammonia products. The ammonia is both excreted in the urine and converted to urea, with urea conversion representing the major form of nitrogen disposal from the body (Figure 2). This urea is produced by the liver and then either travels to the kidneys where it is

Cancer Chemotherapeutics

Chemotherapy-induced hyperammonemia has occasionally been noted in the literature,7, 8, 9 usually associated with hematological malignancies.10 5-Fluorouracil is implicated most often, although others (such as asparaginase)11 are described. However, it is difficult to attribute hyperammonemia to a chemotherapeutic medication in the context of malignancy, which in itself has been reported to result in hyperammonemia independent of treatment.12

Valproic Acid

Although infrequently seen in the inpatient

Conclusions

Hepatic causes of hyperammonemia are by far the most common etiology, but in a patient with normal liver function tests, other causes of elevated ammonia need to be entertained. Likewise, it is also important to realize that elevated ammonia levels in a patient with known hepatic disease need not be hepatic in origin.

Although it might be recommended to check an ammonia level in a patient with mental changes, disorientation, and sleepiness in order to evaluate the cause of the altered mental

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    Funding: The authors have no funding sources related to this publication.

    Conflict of Interest: None of the authors have conflicts of interest regarding the current article.

    Authorship: All authors had access to the relevant data and a role in writing the manuscript.

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