title: Adult-onset ornithine transcarbamylase (OTC) deficiency unmasked by the Atkins' diet.
abstract: OBJECTIVE
  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 24h 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.
authors.affiliation: Liver Institute, Rabin Medical Center, Beilinson Campus, Petah Tiqwa, Israel. gbenari@bezeqint.net
authors.forename: Ziv
authors.initials: Z
authors.lastname: Ben-Ari
authors.forename: Adam
authors.initials: A
authors.lastname: Dalal
authors.forename: Ady
authors.initials: A
authors.lastname: Morry
authors.forename: Silvio
authors.initials: S
authors.lastname: Pitlik
authors.forename: Pierre
authors.initials: P
authors.lastname: Zinger
authors.forename: Jonathan
authors.initials: J
authors.lastname: Cohen
authors.forename: Ittai
authors.initials: I
authors.lastname: Fattal
authors.forename: Ronit
authors.initials: R
authors.lastname: Galili-Mosberg
authors.forename: Debora
authors.initials: D
authors.lastname: Tessler
authors.forename: Ruth Gershoni
authors.initials: RG
authors.lastname: Baruch
authors.forename: Jean-Marc
authors.initials: JM
authors.lastname: Nuoffer
authors.forename: Carlo R
authors.initials: CR
authors.lastname: Largiader
authors.forename: Hanna
authors.initials: H
authors.lastname: Mandel
mesh_terms: D000328:Adult; D017668:Age of Onset; D019943:Amino Acid Substitution; D001928:Brain Diseases, Metabolic / Q000209:etiology; D050528:Diet, Carbohydrate-Restricted / Q000009:adverse effects*; D005260:Female; D006801:Humans; D022124:Hyperammonemia / Q000209:etiology; D007585:Jews / Q000235:genetics; D008297:Male; D008875:Middle Aged; D020125:Mutation, Missense; D009954:Ornithine Carbamoyltransferase / Q000235:genetics; D020163:Ornithine Carbamoyltransferase Deficiency Disease / Q000175:diagnosis* / Q000201:enzymology / Q000235:genetics; D010375:Pedigree
chemical_list: D009954:Ornithine Carbamoyltransferase