The allopurinol load test lacks specificity for primary urea cycle defects but may indicate unrecognized mitochondrial disease
| Autor: | M. S. Tanner, J. M. Land, James R. Bonham, M. Downing, A. Fensom, C. Rittey, P. Guthrie, D. O'Neill, Mark Sharrard, Lynette D. Fairbanks, J. C. Allen, John A. Duley |
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| Rok vydání: | 1999 |
| Předmět: |
Male
medicine.medical_specialty Orotic acid Urea cycle disorder Allopurinol Biology Sensitivity and Specificity Excretion chemistry.chemical_compound Metabolic Diseases Predictive Value of Tests Internal medicine Genetics medicine Humans Urea Child Uridine Genetics (clinical) Orotic Acid Creatinine medicine.diagnostic_test Muscles Infant Newborn Infant Ornithine medicine.disease Mitochondria Endocrinology chemistry Child Preschool Urea cycle Liver biopsy Female medicine.drug |
| Zdroj: | Journal of Inherited Metabolic Disease. 22:174-184 |
| ISSN: | 0141-8955 |
| DOI: | 10.1023/a:1005406205548 |
| Popis: | Thirty-three children ranging from 2 weeks to 12 years of age were selected for allopurinol loading, 16 on the basis of an increased urinary ourotate excretion detected by routine organic acid analysis (group A), and 17 for clinical reasons suggesting a urea cycle defect (group B). The allopurinol load test proved positive in 13 of 16 patients from group A, mean peak orotate 64.0 mumol/mmol creatinine (upper limit of reference range, 13.2) and 11 of 17 patients from group B, mean peak orotate 41.0 mumol/mmol creatinine (upper limit of reference range, 13.2). Thorough investigation of these patients including urinary and plasma amino acid analysis and, in 17 cases, liver biopsy for histology and measurement of ornithine carbamyltransferase (OCT) and carbamyl-phosphate synthetase (CPS) activity failed to identify any evidence of a urea cycle disorder. However, muscle biopsies performed in 11 patients showed some evidence of mitochondrial disease in four cases, two defined on the basis of reduced respiratory chain enzyme activity and two on the basis of mtDNA abnormalities. These findings indicate that an increased excretion of orotate in sick children may not be uncommon and that a positive allopurinol load test result may not indicate a specific inherited urea cycle defect. In addition, these results raise the interesting possibility that defective ureagenesis may be a feature of mitochondrial disease in some individuals. |
| Databáze: | OpenAIRE |
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