Hyperammonemic encephalopathy caused by carnitine deficiency

Abstract

Carnitine is an essential co-factor in fatty acid metabolism. Carnitine deficiency can impair fatty acid oxidation, rarely leading to hyperammonemia and encephalopathy. We present the case of a 35-year-old woman who developed acute mental status changes, asterixis, and diffuse muscle weakness. Her ammonia level was elevated at 276 microg/dL. Traditional ammonia-reducing therapies were initiated, but proved ineffective. Pharmacologic, microbial, and autoimmune causes for the hyperammonemia were excluded. The patient was severely malnourished and her carnitine level was found to be extremely low. After carnitine supplementation, ammonia levels normalized and the patient's mental status returned to baseline. In the setting of refractory hyperammonemia, this case illustrates how careful investigation may reveal a treatable condition.

Figure 1

Stricture at the site of gastrojejunal anastomosis. An endoscopic view from the patient’s esophagus into the gastric remnant is shown. Marked narrowing of the gastrojejunal anastomosis (dotted circle) was noted at the time of endoscopy. The inset depicts a rendition of the patient’s surgical anatomy following gastric bypass

Figure 2

Contrast-enhanced abdominal CT. Shown is a cross-sectional image from the patient’s abdominal CT. The decreased attenuation of the liver in comparison with the spleen is characteristic of diffuse fatty infiltration. The inset displays an example of normal hepatic attenuation

Figure 3

Time course of serum ammonia levels. This graph depicts the patient’s serum ammonia concentration over the course of her hospitalization, with the upper limit of normal indicated by the dotted line. The onset (dark arrows) and termination (light arrows) of relevant clinical interventions are indicated. TPN: total parenteral nutrition

Figure 4

The mitochondrial carnitine transport system. This diagram details the process of carnitine transport from the cytosol to the mitochondrial matrix. Carnitine binds cytosolic fatty acyl-CoA to form acylcarnitine, which is transported into the mitochondrial matrix via the carnitine acylcarnitine translocase (CACT) protein. In the mitochondrial matrix, acyl-CoA undergoes subsequent beta-oxidation, while carnitine is recycled to the cytoplasm. CPT-1: carnitine palmitoyl transferase 1; CPT-2: carnitine palmitoyl transferase 2