AlSubhi Sarah, AlShahwan Saad, AlMuhaizae Mohamed, AlZaidan Hamed, Tabarki Brahim
Division of Neurology, Department of Pediatrics, Prince Sultan Military Medical City, Riyadh, Saudi Arabia.
Department of Neurosciences, King Faisal Specialist Hospital and Research Center, Riyadh, Saudi Arabia.
Eur J Paediatr Neurol. 2017 May;21(3):583-586. doi: 10.1016/j.ejpn.2017.01.010. Epub 2017 Jan 29.
Sepiapterin reductase deficiency is a rare, under-recognized, autosomal recessively inherited disorder of neurotransmitter metabolism.
Five new patients from 3 unrelated Saudi consanguineous families are reported. Symptoms began at 6 months, with delay to diagnosis averaging 8 years. All 5 patients presented with severe symptoms including axial hypotonia, dystonia, and cognitive impairment, associated with hyper-reflexia (4 patients), spasticity (4 patients), bulbar dysfunction (4 patients), and oculogyric crisis (2 patients) with diurnal fluctuation and sleep benefit. Cerebrospinal fluid neurotransmitters analysis showed a typical pattern with increased sepiapterin and increased 7,8-dihydrobiopterin. Analysis of the SPR gene identified 3 novel mutations: c.1A > G, c.370T > C, and c.527C > T. Patient one, with early diagnosis, is currently developing within the normal range. The 4 other patients showed significant improvement in their motor function, but only mild improvement in their cognitive dysfunction.
Our cases illustrate the difficulties in the diagnosis of sepiapterin reductase deficiency in infancy, and the importance of early recognition and management.
蝶呤还原酶缺乏症是一种罕见的、未被充分认识的常染色体隐性遗传的神经递质代谢障碍疾病。
报告了来自3个不相关的沙特近亲家庭的5例新患者。症状始于6个月大时，平均诊断延迟8年。所有5例患者均出现严重症状，包括轴性肌张力减退、肌张力障碍和认知障碍，并伴有反射亢进（4例患者）、痉挛（4例患者）、延髓功能障碍（4例患者）和动眼危象（2例患者），症状有昼夜波动且睡眠时有所缓解。脑脊液神经递质分析显示出一种典型模式，即蝶呤增加和7,8 - 二氢生物蝶呤增加。对SPR基因的分析鉴定出3种新的突变：c.1A > G、c.370T > C和c.527C > T。患者1诊断较早，目前发育正常。其他4例患者的运动功能有显著改善，但认知功能障碍仅略有改善。
我们的病例说明了婴儿期蝶呤还原酶缺乏症诊断的困难，以及早期识别和管理的重要性。
