Hyperammonemia in a patient with late-onset ornithine carbamoyltransferase deficiency.

Ornithine carbamoyltransferase (OTC) deficiency is a urea cycle disorder that causes the accumulation of ammonia, which can lead to encephalopathy. Adults presenting with hyperammonemia who are subsequently diagnosed with urea cycle disorders are rare. Herein, we report a case of a late-onset OTC deficient patient who was successfully treated with arginine, benzoate and hemodialysis. A 59-yr-old man was admitted to our hospital with progressive lethargy and confusion. Although hyperammonemia was suspected as the cause of the patient's mental changes, there was no evidence of chronic liver disease. A plasma amino acid and urine organic acid analysis revealed OTC deficiency. Despite the administration of a lactulose enema, the patient's serum ammonia level increased and he remained confused, leading us to initiate acute hemodialysis. After treatment with arginine, sodium benzoate and hemodialysis, the patient's serum ammonia level stabilized and his mental status returned to normal.

Hyperammonemia in a Patient with Late-Onset Ornithine Carbamoyltransferase Deficiency

Ornithine carbamoyltransferase (OTC) deficiency is a urea cycle disorder that causes the accumulation of ammonia, which can lead to encephalopathy. Adults presenting with hyperammonemia who are subsequently diagnosed with urea cycle disorders are rare. Herein, we report a case of a late-onset OTC deficient patient who was successfully treated with arginine, benzoate and hemodialysis. A 59-yr-old man was admitted to our hospital with progressive lethargy and confusion. Although hyperammonemia was suspected as the cause of the patient's mental changes, there was no evidence of chronic liver disease. A plasma amino acid and urine organic acid analysis revealed OTC deficiency. Despite the administration of a lactulose enema, the patient's serum ammonia level increased and he remained confused, leading us to initiate acute hemodialysis. After treatment with arginine, sodium benzoate and hemodialysis, the patient's serum ammonia level stabilized and his mental status returned to normal.

Aminograms during continuous hemodiafiltration in the treatment of hyperammonemia due to ornithine transcarbamylase deficiency.

BACKGROUND: Hyperammonemia caused by ornithine transcarbamylase (OTC) deficiency can be properly managed by continuous arteriovenous hemodiafiltration (CAVHDF). Removal of amino acids (AA) during CAVHDF has not been thoroughly investigated. AA losses in patients with urea cycle defects due to ornithine transcarbamylase deficiency treated by CAVHDF were analyzed. METHODS: Twelve neonates with elevated serum ammonia levels, confirmed through urine organic acid analysis and serum amino acid studies, were documented to have OTC deficiency. CAVHDF was administered in an attempt to lower serum ammonia concentration. Amino acid analysis of ultrafiltration and serum were performed by liquid chromatography. RESULTS: Serum levels of leucine, isoleucine, methionine, phenylalanine, and tyrosine were significantly lower than acceptable in these patients. Glutamine was the only amino acid that increased significantly, which is clinically relevant to OTC enzyme deficiency. Although the mean serum concentrations of tyrosine and glutamine concentrations were lower in the dialysate, the serum and dialysate concentrations of other amino acids did not differ. CONCLUSION: CAVHDF may induce changes in amino acid metabolism and distribution as well. The requirement of aminogram monitor for amino acid supplementation in urea cycle defect patients is important.

Effects of arginine treatment on nutrition, growth and urea cycle function in seven Japanese boys with late-onset ornithine transcarbamylase deficiency.

BACKGROUND: The aim of this study was to investigate the effects of arginine on nutrition, growth and urea cycle function in boys with late-onset ornithine transcarbamylase deficiency (OTCD). Seven Japanese boys with late-onset OTCD enrolled in this study resumed arginine treatment after the cessation of this therapy for a few years. Clinical presentations such as vomiting and unconsciousness, plasma amino acids and urinary orotate excretion were followed chronologically to evaluate urea cycle function and protein synthesis with and without this therapy. In addition to height and body weight, blood levels of proteins, lipids, growth hormone (GH), insulin-like growth factor-I (IGF-I) and IGF-binding protein -3 (IGFBP-3) were monitored. RESULTS: The frequency of hyperammonemic attacks and urinary orotate excretion decreased significantly following the resumption of arginine treatment. Despite showing no marked change in body weight, height increased gradually. Extremely low plasma arginine increased to normal levels, while plasma glutamine and alanine levels decreased considerably. Except for a slight increase in high-density lipoprotein cholesterol level, blood levels of markers for nutrition did not change. In contrast, low serum IGF-I and IGFBP-3 levels increased to age-matched control levels, and normal urinary GH secretion became greater than the level observed in the controls. CONCLUSION: Arginine treatment is able to reduces attacks of hyperammonemia in boys with late-onset OTCD and to increase their growth.

Unusual causes of hyperammonemia in the ED.

Plasma ammonia measurement is a simple yet important screening in the ED for patients with unexplained stupor or delirium. Acute hyperammonemia is a medical emergency for which immediate steps must be taken to minimize permanent brain damage. Although the most common causes of hyperammonemia are severe abnormal liver function, the absence of liver disease in some cases has been observed. This brief report describes four hyperammonemia cases with normal liver function in the ED. On careful history and speculated examinations, ornithine carbamoyltransferase (OTC) deficiency, hematologic malignancy, and the side effects of valproic acid and 5-fluorouracil (5-FU) were considered. Therapy was first aimed at correcting the hyperammonemia. Once a specific diagnosis was reached, protein restriction, essential amino acid supplementation, efficient chemotherapy, and valproic acid and 5-FU level discontinuance were instituted. In this report, the clinical presentation, pathogenesis, and diagnostic workup for various hyperammonemia causes are discussed. Every EP should understand that the clinical symptoms for hyperammonemia and prognosis are related to early diagnosis.