Very rare metabolic disease with highly variable
clinical expression, including seizures, mental retardation, and
Approximately 10 cases have been reported worldwide.
Autosomal recessive with variable clinical
Dihydropyrimidinase (DHP) catalyzes the
degradation of 5,6-dihydrouracil and 5,6-dihydrothymine to N-carbamyl-β-alanine and N-carbamyl-β-aminoisobutyric acid, respectively. In the
absence of DHP, large quantities of dihydrouracil and dihydrothymine and
moderate amounts of uracil and thymine are excreted in the urine. The
absence of DHP is responsible for a variety of clinical features.
Clinical aspects and urinary metabolite profile
(increased excretion of dihydrouracil, dihydrothymine, uracil, and thymine).
Liver biopsy for measurements of DHP activity confirms the diagnosis.
The small number of patients limits the
experience with the clinical picture. However, a wide range of inconstant
clinical features has been reported, including seizures, extrapyramidal
dyskinesia and pyramidal signs, mental retardation, plagiocephaly (oblique
skull), and facial dysmorphism. Metabolic acidosis may occur.
Obtain a full history of the
seizures and anticonvulsant therapy (efficacy and toxicity). Consider
neurologic consultation in cases with associated extrapyramidal involvement.
Sedative premedication may be helpful in the presence of mental retardation.
Check arterial blood gases and postpone elective surgery until metabolic
acidosis (rare) is corrected. Check for difficult airway management in the
presence of facial dysmorphism.
No literature is available. However,
difficult airway management should be expected to be difficult. Depending on
the kind of the procedure, intraoperative arterial or venous blood gas
analysis is recommended.
Avoid potentially epileptogenic drugs
(e.g., methohexital, ketamine, enflurane, atracurium, cisatracurium,
meperidine). In cases with associated extrapyramidal manifestations, avoid
drugs with antidopaminergic effects (e.g., droperidol, domperidone,
metoclopramide). Consider interaction between antiepileptic treatment and
anesthetic drugs. Muscle relaxants should be avoided until airway is
Dihydropyrimidine Dehydrogenase Deficiency: Genetic disorder with
a high phenotypic variability, ranging from asymptomatic to developmental
delay and seizures. Increased toxicity of 5-fluorouracil.
Duran M, Rovers P, De Bree PK, et al: Dihydropyrimidinuria: A
new inborn error of pyrimidine metabolism. J Inherit Metab Dis
Hamajima N, Kouwaki M, Vreken P, et al: Dihydropyrimidinase deficiency:
Structural organization, chromosomal localization, and mutation analysis of
the human dihydropyrimidinase gene. Am J Hum Genet
Van Gennip AH, De Abreu RA, Van Lenthe H, et al: Dihydropyrimidinase
deficiency: Confirmation of the enzyme defect in dihydropyrimidinuria. J Inherit
Metab Dis 20:339, 1997.