title: Dihydropyrimidine dehydrogenase deficiency in two malaysian siblings with abnormal MRI findings.
abstract: Dihydropyrimidine dehydrogenase (DPD) deficiency is an autosomal recessive disorder of the pyrimidine metabolism. Deficiency of this enzyme leads to an accumulation of thymine and uracil and a deficiency of metabolites distal to the catabolic enzyme. The disorder presents with a wide clinical spectrum, ranging from asymptomatic to severe neurological manifestations, including intellectual disability, seizures, microcephaly, autistic behavior, and eye abnormalities. Here, we report on an 11-year-old Malaysian girl and her 6-year-old brother with DPD deficiency who presented with intellectual disability, microcephaly, and hypotonia. Brain MRI scans showed generalized cerebral and cerebellar atrophy and callosal body dysgenesis in the boy. Urine analysis showed strongly elevated levels of uracil in the girl and boy (571 and 578 mmol/mol creatinine, respectively) and thymine (425 and 427 mmol/mol creatinine, respectively). Sequence analysis of the DPYD gene showed that both siblings were homozygous for the mutation c.1651G>A (pAla551Thr).
authors.affiliation: Department of Genetics, Kuala Lumpur Hospital, Kuala Lumpur, Malaysia.
authors.forename: Bee Chin
authors.initials: BC
authors.lastname: Chen
authors.affiliation: School of Medical Sciences, University of Sciences Malaysia, Kelantan, Malaysia.
authors.forename: Rowani
authors.initials: R
authors.lastname: Mohd Rawi
authors.affiliation: Laboratory of Genetic Metabolic Diseasess, University of Amsterdam, Amsterdam, The Netherlands.
authors.forename: Rutger
authors.initials: R
authors.lastname: Meinsma
authors.affiliation: Laboratory of Genetic Metabolic Diseasess, University of Amsterdam, Amsterdam, The Netherlands.
authors.forename: Judith
authors.initials: J
authors.lastname: Meijer
authors.affiliation: Department of Pediatrics, Academic Medical Center, University of Amsterdam, Amsterdam, The Netherlands.
authors.forename: Raoul C M
authors.initials: RC
authors.lastname: Hennekam
authors.affiliation: Laboratory of Genetic Metabolic Diseasess, University of Amsterdam, Amsterdam, The Netherlands.
authors.forename: André B P
authors.initials: AB
authors.lastname: van Kuilenburg
keywords: Dihydropyrimidine dehydrogenase deficiency; MRI abnormality; Protein folding