| An OTC deficiency 'phenocopy' in association with Klinefelter syndrome. | |
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MedLine Citation:
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PMID: 17186414 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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Late-onset urea cycle disorder in a 20-month-old boy is unusually associated with Klinefelter syndrome with a 47XXY karyotype. We record the typical clinical and biochemical findings of ornithine transcarbamylase (OTC) deficiency in a young boy with a short history of recurrent vomiting, self mutilating behaviour, lethargy, ataxia and seizures. Laboratory studies showed hyperammonaemia and orotic aciduria, with normal citrulline and other urea cycle amino acids. Unfortunately, a liver biopsy for OTC activity measurement was refused by the parents. A rapid reversal of phenotype was seen on the introduction of a low-protein diet with accompanying benzoate and phenylbutyrate administration. Linkage studies suggested the inheritance of two X chromosomes, which was confirmed by karyotype analysis. Sequencing of all exons and immediate splice site regions revealed no sequence alterations in these sections of the OTC gene. A search for skewing of X-inactivation in the liver was not possible but we did show a random pattern of X-inactivation in leukocytes. The possibility of maternal X chromosome iso-disomy in our patient was discounted by microsatellite analysis, which revealed the inheritance of two independent X chromosomes. Mutation analysis in the OTC gene has shown that approximately 20% of patients with liver biopsy confirmed OTC deficiency do not have mutations in the coding or immediate splice-site sequences of this gene. Their classification as OTC phenocopies remains speculative, awaiting clarification of the underlying DNA alteration. We report on the novel association of OTC deficiency and Klinefelter syndrome with the additional interest of a probable unusual genetic defect underlying the OTC abnormality. |
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Authors:
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L Swarts; F Leisegang; E P Owen; H E Henderson |
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Publication Detail:
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Type: Case Reports; Journal Article Date: 2006-12-20 |
Journal Detail:
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Title: Journal of inherited metabolic disease Volume: 30 ISSN: 1573-2665 ISO Abbreviation: J. Inherit. Metab. Dis. Publication Date: 2007 Feb |
Date Detail:
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Created Date: 2007-01-19 Completed Date: 2007-03-13 Revised Date: 2007-03-21 |
Medline Journal Info:
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Nlm Unique ID: 7910918 Medline TA: J Inherit Metab Dis Country: Netherlands |
Other Details:
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Languages: eng Pagination: 101 Citation Subset: IM |
Affiliation:
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Division of Chemical Pathology, University of Cape Town and NHLS, Cape Town, South Africa. |
Export Citation:
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| MeSH Terms | |
Descriptor/Qualifier:
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Chromosomes, Human, X DNA Mutational Analysis Humans Infant Karyotyping Klinefelter Syndrome / complications*, diagnosis*, genetics Male Ornithine Carbamoyltransferase / genetics Ornithine Carbamoyltransferase Deficiency Disease / complications*, diagnosis*, genetics Phenotype X Chromosome Inactivation |
| Chemical | |
Reg. No./Substance:
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EC 2.1.3.3/Ornithine Carbamoyltransferase |
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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