Department of Paediatrics, Derby Hospitals National Health Service Foundation Trust, Derby, United Kingdom.
Pediatr Neurol. 2012 Mar;46(3):178-81. doi: 10.1016/j.pediatrneurol.2011.12.005.
An 8-month-old girl, born to consanguineous parents, presented with developmental delay, decreased muscle tone, disinterest in her surroundings, and sleepiness. Tests revealed a marked excretion of thymine with significantly increased uracil excretion in the urine, indicating a pyrimidine catabolic disorder, i.e., dihydropyrimidine dehydrogenase deficiency. Plasma endogenous purines confirmed elevated plasma thymine (21 μmol/L) and uracil (29 μmol/L), also consistent with dihydropyrimidine dehydrogenase deficiency. Purine mutation analysis confirmed complete dihydropyrimidine dehydrogenase deficiency with a 16 [ corrected] base pair homozygous deletion in exon 16, corresponding to DPYD c.2043-2058del. Cranial magnetic resonance imaging at 14 months indicated severe hypomyelination with gliosis. Her basal ganglia were also involved. At age 15 months, she was hospitalized for aspiration pneumonia and seizures, and also manifested hepatosplenomegaly. White cell enzymes revealed a marked deficiency of β-galactosidase activity (4 μmol/g/hour) in white cells and an elevated chitotriosidase activity (443 μmol/L/hour) in plasma indicating GM(1) gangliosidosis. Mutation analysis confirmed c.841C>T (p.His281Tyr) homozygosity for GM(1) gangliosidosis. She died at age 19 months.
一名 8 月龄女婴，由近亲父母所生，表现为发育迟缓、肌张力降低、对周围环境不感兴趣和嗜睡。检查结果显示尿液中胸腺嘧啶排泄明显增加，尿嘧啶排泄显著增加，表明嘧啶代谢紊乱，即二氢嘧啶脱氢酶缺乏症。血浆内源性嘌呤证实血浆胸苷（21 μmol/L）和尿嘧啶（29 μmol/L）升高，也符合二氢嘧啶脱氢酶缺乏症。嘌呤基因突变分析证实完全性二氢嘧啶脱氢酶缺乏症，第 16 外显子发生 16 [校正]个碱基的纯合缺失，对应 DPYD c.2043-2058del。14 月龄时的颅脑磁共振成像显示严重的脑白质发育不良伴胶质增生。基底节也受累。15 月龄时，因吸入性肺炎和癫痫发作住院，同时伴有肝脾肿大。白细胞酶显示白细胞β-半乳糖苷酶活性显著缺乏（4 μmol/g/hour），血浆中壳三糖苷酶活性升高（443 μmol/L/hour），提示 GM(1)神经节苷脂贮积症。突变分析证实 GM(1)神经节苷脂贮积症 c.841C>T（p.His281Tyr）纯合。她于 19 月龄时死亡。
