Hereditary orotic aciduria is an extremely rare autosomal recessive disorder characterized by growth retardation, increased urinary excretion of orotic acid and anemia. It is caused by deficiency of uridine 5'-monophosphate (UMP) synthase, which is encoded by the UMPS gene. So far, the only mutations reported in this gene appear to be three missense variants described by Suchi M et al (1997, PMID: 9042911, free full text available).
However it is important to highlight that increased excretion of orotic acid in urine also occurs in inborn errors of the mitochondrial ornithine/citrulline transporter, arginase, argininosuccinate synthetase, and argininosuccinate lyase. Increased orotic acid excretion is also found in a number of hypoargininemic states, such as lysinuric protein intolerance. Another clinical entity to be taken in mind in the differential diagnosis of orotic aciduria should be congenital disorder of glycosylation type Ia (CDG1A), which is caused by mutations in the PMM2 gene. In the infantile multisystem stage of CDG1A infants show axial hypotonia, hyporeflexia, esotropia and developmental delay; feeding problems, vomiting and diarrhea with failure to thrive, and impaired growth. Two distinct clinical presentations are observed: the first is a non-fatal neurologic form with strabismus, psychomotor retardation, and cerebellar hypoplasia in infancy followed by neuropathy and retinitis pigmentosa in the first or second decade; the second is a neurologic-multivisceral form with approximately 20% mortality in the first year of life.
Suchi M et al (1997, PMID: 9042911, free full text available)
Salerno C et al (2002, PMID: 12450653)
