Chen Bee Chin, Mohd Rawi Rowani, Meinsma Rutger, Meijer Judith, Hennekam Raoul C M, van Kuilenburg André B P
Department of Genetics, Kuala Lumpur Hospital, Kuala Lumpur, Malaysia.
School of Medical Sciences, University of Sciences Malaysia, Kelantan, Malaysia.
Mol Syndromol. 2014 Dec;5(6):299-303. doi: 10.1159/000366074. Epub 2014 Sep 25.
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).
二氢嘧啶脱氢酶（DPD）缺乏症是一种嘧啶代谢的常染色体隐性疾病。这种酶的缺乏会导致胸腺嘧啶和尿嘧啶的积累以及分解代谢酶下游代谢产物的缺乏。该疾病临床表现广泛，从无症状到严重的神经学表现，包括智力残疾、癫痫发作、小头畸形、自闭症行为和眼部异常。在此，我们报告一名11岁马来西亚女孩及其6岁弟弟患有DPD缺乏症，表现为智力残疾、小头畸形和肌张力减退。脑部磁共振成像扫描显示男孩存在广泛性大脑和小脑萎缩以及胼胝体发育不全。尿液分析显示女孩和男孩的尿嘧啶水平（分别为571和578 mmol/mol肌酐）以及胸腺嘧啶水平（分别为425和427 mmol/mol肌酐）均显著升高。DPYD基因序列分析显示，这对姐弟均为c.1651G>A（p.Ala551Thr）突变的纯合子。
