Case report of a 1-year old girl with β-ureidopropionase deficiency and development of cystic encephalomalacia

Introduction: The β-ureidopropionase deficiency (OMIM #613161) is a rare metabolic disorder, involving the third enzyme of the pyrimidine degradation pathway. Endproducts of this pathway are β-alanine and β-aminoisobutyric-acid. Both compounds are regarded to act as inhibitory neurotransmitters in the central nervous system (van Kuilenberg ABP et al. 2004). In β-ureidopropionase deficiency both compounds are missing. To our knowledge 11 patients have been published so far with β-ureidopropionase deficiency. Four asymptomatic patients from Japan were identified by large-scale screening in 24 000 newborns. All four patients remained asymptomatic during follow-up. Of the remaining seven patients, one had multiple urogenital and colorectal malformations, without neurological symptoms. The other six patients had various combinations of neurological symptoms like autistic behaviour, seizures, hypotonia, dystonia or global retardation.

Case report: We present a 1-year old girl with an unremarkable perinatal history. She reached regular developmental milestones. At the age of 11 months the girl suffered from an episode with fever and diarrhea. On the second day of illness she developed focal seizures. Cloni at the right corner of the mouth preceded a status epilepticus refractory to antiepileptic medication. Finally the infant was intubated and ventilated and received thiopental. MRI revealed a generalised edema of the brain. The metabolic diagnostic work-up raised suspicion for a β-ureidopropionase deficiency. The diagnosis was confirmed by the identification of a mutation in the UBP1-gen. Brain MRI after 2 month displayed extended cystic encephalomalacia.

Discussion: Defects in the degradation of pyrimidine bases can cause a wide range of neurologic symptoms, like seizures, global retardation, hypotonia oder dystonia. Therefore it is important to include these disorders in the diagnostic work-up. The mechanisms underlying the clinical symptoms are currently not known. In patients with β-ureidopropionase deficiency chemotherapeutic agents like 5-fluorouracil should be avoided, because of the risk of developing severe 5-fluorouracil toxicity.