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At a glance

Very rare metabolic disease with highly variable clinical expression, including seizures, mental retardation, microcephaly, and craniofacial anomalies. Other clinical features include early infantile onset of severe neurologic involvement with feeding problems to a later onset accompanied with mild intellectual disability, even asymptomatic individuals. There is an increased risk of pyrimidine degradation defects and severe 5-fluorouracil toxicity.


Dihydropyrimidinuria; DPH Deficiency; DPYS Deficiency.


Approximately 10 cases have been reported worldwide.

Genetic inheritance

Autosomal recessive with variable clinical phenotype. It is caused by an homozygous or compound heterozygous mutation in the DPYS gene on chromosome 8q22.


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.

Clinical aspects

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.

Precautions before anesthesia

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.

Anesthetic considerations

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.

Pharmacological implications

Avoid potentially epileptogenic drugs (eg, methohexital, ketamine, enflurane, atracurium, cisatracurium, meperidine). In cases with associated extrapyramidal manifestations, avoid drugs with antidopaminergic effects (eg, droperidol, domperidone, metoclopramide). Consider interaction between antiepileptic treatment and anesthetic drugs. Muscle relaxants should be avoided until airway is secured. Finally, affected individuals with a complete or partial deficiency have an increased risk of developing severe toxicity after administration of the anticancer drug 5-fluorouracil (5-FU).

Other condition to be considered

  • Dihydropyrimidine Dehydrogenase Deficiency: Genetic disorder with a high phenotypic variability, ranging from asymptomatic to developmental delay and seizures. Increased toxicity of ...

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