Adult-onset ornithine transcarbamylase (OTC) deficiency unmasked by the Atkins’ diet
| Autor: | Ady Morry, Pierre Zinger, Carlo R. Largiadèr, Jonathan Cohen, Hanna Mandel, Ziv Ben-Ari, Silvio Pitlik, Jean-Marc Nuoffer, Adam Dalal, Ruth Gershoni Baruch, Ronit Galili-Mosberg, Ittai Fattal, Debora Tessler |
|---|---|
| Rok vydání: | 2010 |
| Předmět: |
Adult
Male food.diet Genetic counseling Encephalopathy Ornithine transcarbamylase Ornithine Carbamoyltransferase Deficiency Disease Mutation Missense Physiology chemistry.chemical_compound Diet Carbohydrate-Restricted food Atkins diet Medicine Missense mutation Humans Hyperammonemia Age of Onset Ornithine Carbamoyltransferase Genetics Hepatology business.industry Brain Diseases Metabolic Ornithine Middle Aged medicine.disease Pedigree OTC chemistry Amino Acid Substitution Jews Deficiency Female business |
| Zdroj: | ResearcherID |
| ISSN: | 0168-8278 |
| DOI: | 10.1016/j.jhep.2009.11.014 |
| Popis: | 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 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. |
| Databáze: | OpenAIRE |
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