沙特一名儿童生物素-硫胺素反应性基底节疾病的病例报告：是否建议进行扩展的基因家族研究？
A case report of biotin-thiamine-responsive basal ganglia disease in a Saudi child: Is extended genetic family study recommended?
作者信息
Aljabri Mohammad F, Kamal Naglaa M, Arif Moinuddin, AlQaedi Asrar M, Santali Enas Y M
机构信息
Alhada Armed Forces Hospital, Taif, Saudi Arabia Faculty of Medicine, Cairo University, Cairo, Egypt Pediatric Consultant, Hera General Hospital, Holly Makkah, Saudi Arabia.
出版信息
Medicine (Baltimore). 2016 Oct;95(40):e4819. doi: 10.1097/MD.0000000000004819.
BACKGROUND
Biotin-thiamine-responsive basal ganglia disease (BTRBGD) is a neurometabolic autosomal recessive (AR) disorder characterized by subacute encephalopathy with confusion, convulsions, dysarthria, and dystonia. The disease is completely reversible if treated early with biotin and thiamine, and can be fatal if left untreated.We herein present our experience with in an extended family study of an index case of BTRBGD aiming to support its AR mode of inheritance, diagnose asymptomatic and missed symptomatic cases, and provide family screening with proper genetic counseling.
METHODS
An index case of BTRBGD and his family underwent thorough clinical and radiological assessment along with genetic molecular testing.
RESULTS
Two-and-half years old Saudi male child whose parents are consanguineous fulfilled the clinical and magnetic resonance imaging (MRI) criteria of BTRBGD. He was proved by molecular genetic testing to have homozygous mutation of c.1264A>G (p.Thr422Ala) in the SLC19A3 gene of BTRBGD. Extended clinical, radiological, and genetic family study revealed 2 affected members: a neglected symptomatic cousin with subtle neurological affection and an asymptomatic brother carrying the disease mutation in homozygous status. Heterozygous pattern was detected in his parents, his grandma and grandpa, his aunt and her husband, 2 siblings, and 1 cousin while 1 sibling and 2 cousins were negative to this mutation.Treatment of the patient and his diseased cousin with biotin and thiamine was initiated with gradual improvement of symptoms within few days. Treatment of his asymptomatic brother was also initiated.
CONCLUSION
BTRBGD requires high index of suspicion in any child presenting with unexplained subacute encephalopathy, abnormal movement, and characteristic MRI findings. Extended family study is crucial to diagnose asymptomatic diseased cases and those with subtle neurological symptoms.
背景
生物素-硫胺素反应性基底节疾病（BTRBGD）是一种神经代谢性常染色体隐性（AR）疾病，其特征为亚急性脑病，伴有意识模糊、惊厥、构音障碍和肌张力障碍。如果早期用生物素和硫胺素治疗，该疾病可完全逆转，若不治疗则可能致命。我们在此介绍对一例BTRBGD索引病例进行的大家庭研究经验，旨在支持其AR遗传模式，诊断无症状和漏诊的有症状病例，并为家庭筛查提供适当的遗传咨询。
方法
对一例BTRBGD索引病例及其家族进行了全面的临床和影像学评估以及基因分子检测。
结果
一名2岁半的沙特男童，其父母为近亲，符合BTRBGD的临床和磁共振成像（MRI）标准。分子基因检测证实他在BTRBGD的SLC19A3基因中有c.1264A>G（p.Thr422Ala）的纯合突变。扩展的临床、影像学和基因家族研究发现2名受影响成员：一名被忽视的有轻微神经病变的有症状表亲，以及一名无症状的兄弟，其携带该疾病突变的纯合状态。在他的父母、祖父母、姑姑和姑父、2名兄弟姐妹以及1名表亲中检测到杂合模式，而1名兄弟姐妹和2名表亲对该突变呈阴性。对该患者及其患病表亲开始用生物素和硫胺素治疗，症状在数天内逐渐改善。对其无症状的兄弟也开始了治疗。
结论
对于任何出现不明原因的亚急性脑病、异常运动和特征性MRI表现的儿童，BTRBGD都需要高度怀疑。大家庭研究对于诊断无症状患病病例和有轻微神经症状的病例至关重要。
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