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Very rare metabolic disease with highly variable clinical expression, including seizures, mental retardation, and craniofacial anomalies.


Approximately 10 cases have been reported worldwide.

Autosomal recessive with variable clinical phenotype.

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 secured.

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 14:367, 1991.  [PubMed: 1770794]
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 63:717, 1998.  [PubMed: 9718352]
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.

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