The clinical features are assumed to be related to pyrimidine nucleotide depletion. The onset of symptoms has usually occurred in the first few months of life. Failure to thrive, developmental retardation, cardiac malformations, bilateral strabismus, sparse hair, inability to sit unaided, and gross crystalluria, occasionally with ureteric obstruction, have been general findings. Renal function is generally normal. Infections have occurred in some instances, associated with abnormalities of immune function.
Heterozygotes show mild orotic aciduria but are otherwise unaffected.
This is an extremely rare disorder and has been identified in 14 cases widely distributed geographically, including caucasians, orientals, Polynesians, American Indians and negroes. The enzyme defect is inherited in an autosomal recessive fashion and has been confirmed in liver, fibroblasts, lymphoblasts, erythrocytes and leucocytes from affected individuals. Cells from patients with the mutant enzyme express the UMPS gene at normal levels and produce a stable mRNA transcript identical in size and quantity to mRNA of control cells. Urinary orotic acid may be measured colorimetrically, but blanks must be included since falsely raised values can be produced by histidine, septrin etc. However, OPRT is unstable even in frozen erythrocytes, and although ODC is less so, both enzyme activities decrease with erythrocyte age.