Center for Human Genetics and Laboratory Diagnostics, Dr. Klein, Dr. Rost and Colleagues

DPD Deficiency (Hereditary Thymine Uraciluria) [79.9]

OMIM numbers: 274270, 612779 (DP[Y]D)

Dipl.-Biol. Birgit Busse

Scientific Background

A genetically-caused DPD deficiency leads to disorders in the pyrimidine metabolism. Patients with two mutations in both alleles of the DPD gene in compound heterozygous or homozygous form frequently show developmental disorders, seizures, short stature, microcephaly, dysmorphia and autistic behaviour. Severity of the signs in patients described in the literature varies considerably. Therefore, a clear correlation between genotype and phenotype could so far not be shown. In addition, the pathomechanismus causing the disease has not yet been characterized well. Regarding laboratory diagnostics, thymine uraciluria specifically indicates a DPD deficiency.

For patients with this clinical picture, chemotherapy with 5-Fluorouracil (5-FU) and its prodrugs is contra-indicated (see 5-FU Therapy).