Orotic aciduria syndrome ... (Orotic aciduria Syndrome) - Gen UMPS

The orotic aciduria is a process characterized by the presence of crystalluria megaloblastic anemia and orotic acid, often associated with some degree of mental and physical disabilities. These characteristics respond to replacement therapy pyrimidine, and most cases have a good prognosis. A minority of cases have other abnormalities such as congenital malformations and immune deficiencies, which can alter the prognosis. Phenotypic characteristics of orotic aciduria are megaloblastic anemia, unresponsive to therapy with vitamin B12 and folic acid, hypochromic microcytic with which persists with iron administration or pyridoxine; high amounts of orotic acid in urine, which are corrected with the administration of uridylic acid and cytidylic acid.

This process is due to mutations in the gene UMPS, located on the long arm of chromosome 3 (3q13). This gene encodes a uridine 5'-monophosphate synthase, a bifunctional enzyme possessing two activities: orotate phosphoribosyltransferase (OPRT) and OMP decarboxylase (ODC). The first metabolic reaction is carried out by orotate phosphoribosyltransferase enzyme, which converts orotic acid in orotidine-5'-monophosphate. Subsequently, the enzyme that converts OMP decarboxylase orotidine-5'-monophosphate in uridine monophosphate. Its role is exercised in the last two steps in the biosynthesis of uridine monophosphate (UMP).

The orotic aciduria is inherited as an autosomal recessive pattern, which means that both copies of the gene in every cell must have mutations for alteration is expressed. The parents of an individual with an autosomal recessive disease have a copy of the mutated gene, but usually show no signs and symptoms of the disease.

Tests in IVAMI: in IVAMI perform detection of mutations associated with orotic aciduria syndrome, by complete PCR amplification of the exons of the gene UMPS, and subsequent sequencing.

Samples recommended: EDTA blood collected for separation of blood leukocytes, or impregnated sample card with dried blood (IVAMI may mail the card to deposit the blood sample).