Adult-onset ornithine transcarbamylase (OTC) deficiency unmasked by the Atkins’ diet

• Published in: Journal of hepatology Vol. 52; no. 2; pp. 292 - 295
• Main Authors: Ben-Ari, Ziv, Dalal, Adam, Morry, Ady, Pitlik, Silvio, Zinger, Pierre, Cohen, Jonathan, Fattal, Ittai, Galili-Mosberg, Ronit, Tessler, Debora, Baruch, Ruth Gershoni, Nuoffer, Jean-Marc, Largiader, Carlo R, Mandel, Hanna
• Format: Journal Article
• Language: English
• Published: Kidlington Elsevier B.V 01.02.2010; Elsevier
• Subjects: Adult; Age of Onset; Amino Acid Substitution; Atkins diet; Biological and medical sciences; Brain Diseases, Metabolic - etiology; Deficiency; Diet, Carbohydrate-Restricted - adverse effects; Female; Gastroenterology and Hepatology; Gastroenterology. Liver. Pancreas. Abdomen; Humans; Hyperammonemia - etiology; Jews - genetics; Male; Medical sciences; Middle Aged; Mutation, Missense; Ornithine Carbamoyltransferase - genetics; Ornithine Carbamoyltransferase Deficiency Disease - diagnosis; Ornithine Carbamoyltransferase Deficiency Disease - enzymology; Ornithine Carbamoyltransferase Deficiency Disease - genetics; OTC; Pedigree; computed tomography; electroencephalograph; CT; Atkins diet; Deficiency; EEG; ornithine transcarbamylase; PCR; polymerase chain reaction; OTC; Human; Diet; Aminoacid; Gastroenterology; Adult; Ornithine
• ISSN: 0168-8278; 1600-0641
• DOI: 10.1016/j.jhep.2009.11.014

Background & Aims Late-onset symptoms of urea-cycle disorder may lead to a life-threatening disease which is often undetected. We report the clinical and metabolic manifestations of acute hyperammonemic encephalopathy in a 47-year-old asymptomatic man with ornithine transcarbamylase (OTC) deficiency. The hyperammonemic encephalopathy was unmasked by a high-protein Atkins diet. Methods Genetic analysis of the patient’s family, 89 unrelated Ashkenazi Jewish and 50 unrelated Europeans subjects was performed using polymerase chain reaction amplification and DNA sequencing of the OTC gene. Results Treatment with hemodialysis, provision of adequate calories to prevent catabolism, and protein elimination for 24 h followed by protein restriction and ammonia scavenging medications effectively lowered the patient’s plasma ammonia level and resulted in full recovery. Genetic analysis of the OTC gene revealed a novel hemizygous missense mutation in exon 5 (c.477T>G), leading to an isoleucine-to-methionine substitution in codon 159 (Ile159Met). Further genetic analysis of the patient’s family yielded the mutation in many of them, although findings were negative in 89 unrelated Ashkenazi Jewish and 50 unrelated Europeans subjects. Conclusions This is the first reported case of an adult urea-cycle defect unmasked by the Atkins diet. Measurements of serum ammonia level must be part of the basic work-up in all patients presenting with encephalopathy of unknown origin even in the absence of liver dysfunction. Awareness of this important association can contribute to prompt diagnosis and life-saving treatment. Correct diagnosis is also important to prevent future recurrences and to provide genetic counselling for family members.