Pyridoxal phosphate-responsive seizures in a patient with cerebral folate deficiency (CFD) and congenital deafness with labyrinthine aplasia, microtia and microdontia (LAMM)
Pyridoxal phosphate-responsive seizures in a patient with cerebral folate deficiency (CFD) and congenital deafness with labyrinthine aplasia, microtia and microdontia (LAMM)
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DOI：
10.1016/j.ymgme.2011.05.019
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发表时间：
2011-11-01
影响因子：
3.8
通讯作者：
Blau, Nenad
中科院分区：
文献类型：
--
作者：
Dill, Patricia;Schneider, Jacques;Blau, Nenad
我们报告了一个8岁的男孩叶酸受体α (FR α)缺陷和先天性耳聋迷路发育不全，小畸形和小牙畸形（LAMM综合征）。这两种情况都是异常罕见的常染色体隐性遗传病，定位于11q13。我们的患者在FOLIO基因（p.R204X）和FGF3基因（p.C50X）中发现了新的纯合无义突变。FR α缺陷是一种脑特异性叶酸运输障碍，伴有脑叶酸缺乏症（CFD），导致进行性神经系统症状，而LAMM综合征是一种完全畸形的疾病，具有正常的身体生长和认知发育。我们的病人在儿童早期表现为先天性耳聋，张力低下，呼吸困难和共济失调。6岁时出现难治性癫痫，8岁时临床恶化为呼吸骤停和重度呼吸亢进。与先前发表的FOLR1基因缺陷患者相反，我们的患者表现为脑脊液中l-多巴代谢异常，3- o -甲基多巴含量高。口服叶酸治疗后，男孩恢复了意识，而癫痫只能通过额外的吡哆醛5'-磷酸（PLP）才能成功控制。这篇报道指出了脑脊液叶酸检查在患有无法解释的进行性神经系统症状的儿童中的重要性，即使畸形综合征明显存在，并建议在叶酸无反应性癫痫发作中应用PLP进行试验。(C) 2011爱思唯尔公司版权所有。
We present an 8-year-old boy with folate receptor alpha (FR alpha) defect and congenital deafness with labyrinthine aplasia, microtia and microdontia (LAMM syndrome). Both conditions are exceptionally rare autosomal recessive inherited diseases mapped to 11q13. Our patient was found to have novel homozygous nonsense mutations in the FOLIO gene (p.R204X), and FGF3 gene (p.C50X). While the FR alpha defect is a disorder of brain-specific folate transport accompanied with cerebral folate deficiency (CFD) causing progressive neurological symptoms, LAMM syndrome is a solely malformative condition, with normal physical growth and cognitive development.Our patient presented with congenital deafness, hypotonia, dysphygia and ataxia in early childhood. At the age of 6 years he developed intractable epilepsy, and deteriorated clinically with respiratory arrest and severe hypercapnea at the age of 8 years. In contrast to the previously published patients with a FOLR1 gene defect, our patient presented with an abnormal L-dopa metabolism in CSF and high 3-O-methyl-dopa. Upon oral treatment with folinic acid the boy regained consciousness while the epilepsy could be successfully managed only with additional pyridoxal 5'-phosphate (PLP).This report pinpoints the importance of CSF folate investigations in children with unexplained progressive neurological presentations, even if a malformative syndrome is obviously present, and suggests a trial with PLP in folinic acid-unresponsive seizures. (C) 2011 Elsevier Inc. All rights reserved.