Ornithine transcarbamylase (OTC) deficiency (MIM 311250) is a rare X-linked recessive disorder. Females also frequently manifest the condition, presumably due to non-random X chromosome inactivation in their liver cells. Deficiency of OTC causes a defect in the urea cycle and results in hyperammonemia, leading to lethargy, vomiting, coma and premature death. The clinical presentation is variable. In males there are generally accepted to be two forms of OTC deficiency - a neonatal form, where patients have severe hyperammonemia which is fatal in the first few days of life and a late onset form which occurs at any point after this initial neonatal period and can be exacerbated by infection, metabolic stress or excessive protein intake. Female carriers can also experience this full range of clinical symptoms, varying from apparently unaffected to neonatal death.
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When requesting this test please use the referral form provided. Please also refer to any additional information provided for this test.
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Prior to genetic analysis, clinically affected patients should, wherever possible, be confirmed as having OTC deficiency by enzyme analysis on a liver biopsy, or by finding elevated orotic acid levels by biochemical analysis. Allopurinol or protein load tests can be used to indicate female carrier status, but these are not always conclusive. Mutation analysis can be requested in the affected proband of a family, please supply details of biochemical testing undertaken, clinical details and any relevant pedigree. If there is no sample available from an affected individual testing can be undertaken in the mother of an affected child (- however, it should be noted that, unless there are additional affected family members they are not necessarily mutation carriers). The OTC gene (Xp21.1) consists of 10 exons and family specific mutations are found throughout the gene, although some recurrent mutations at CpG sites in exons 1, 3, 5 and 9 are reported and some late onset specific mutations are known. A whole gene deletion accounts for approximately 10% of OTC cases. Entire gene deletions account for ~10% of neonatal OTC cases and are tested for by MLPA analysis in both males and females. This is then followed by mutation screening of the gene by direct sequence analysis of the 10 exons and intron-exon boundaries. This testing strategy detects approximately 84% of mutations in patients with enzymatically confirmed OTC deficiency.
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Great Ormond Street Hospital NE Thames Regional Genetics Service Laboratories
Great Ormond Street Hospital for Children
37 Queen Square
1ml EDTA neonates, 5ml EDTA adults
Deletion screen - 20 days; gene screen - 40 days
Disease / group
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Prenatals must be arranged in advance, through a Clinical Genetics department if possible. Amniotic fluid or CV samples should be sent to Cytogenetics for dissecting and culturing, with instructions to forward the sample to the Regional Molecular Genetics laboratory for analysis