Molecular Pathology of OTC Deficiency

The diagnosis of OTC deficiency is made by assay of OTC activity in the liver of an affected proband, or by measurement of orotic acid +/orotidine excretion in the urine after a protein or amino acid load or after a single dose of allopurinol in a proband or suspected carrier (see Chapter 8 for details). If prenatal diagnosis is desired, these approaches are less useful. OTC activity is not expressed in amniocytes and there are no unusual metabolites found in the amniotic fluid in OTC deficiency. Fetal liver biopsies are possible in order to assay urea cycle enzymes but are quite risky to the pregnancy(219–221). Thus molecular genetic approaches have been developed to solve this problem.