PDF(Pubmed)
Abstract：
Biotin-thiamine-responsive basal ganglia disease (BTBGD) is a rare autosomal recessive neurometabolic disorder that is caused by biallelic pathogenic SLC19A3 variants and is characterized by subacute encephalopathy associated with confusion, convulsions, dysphagia, dysarthria, or other neurological manifestations.
A retrospective review of the data registry in Kuwait Medical Genetics Center for all cases diagnosed clinically and radiographically and confirmed genetically with BTBGD.
Twenty one cases from 13 different families were diagnosed with BTBGD in Kuwait. Most cases (86%) presented with confusion, dystonia, convulsions, or dysarthria, while three individuals were diagnosed pre-symptomatically during familial targeted genetic screening. Symptoms resolved completely within 2-week of treatment in two-thirds of the symptomatic cases but progressed in six of them to a variety of severe symptoms including severe cogwheel rigidity, dystonia and quadriparesis due to delayed presentation and management. Neuroradiological findings of the symptomatic cases revealed bilateral central changes in the basal ganglia. Two novel homozygous missense SLC19A3 variants were detected in a Kuwaiti and a Jordanian individuals, in addition to the previously reported Saudi founder homozygous variant, c.1264A > G; p.(Thr422Ala) in the remaining cases. Age of diagnosis ranged from newborn to 32 years, with a median age of 2-3 years. All cases are still alive receiving high doses of biotin and thiamine.
This is the first study reporting the phenotypic and genotypic spectrum of 21 individuals with BTBGD in Kuwait and describing two novel SLC19A3 variants. BTBGD is a treatable neurometabolic disease that requires early recognition and treatment initiation. This study highlights the importance of performing targeted molecular testing of the founder variant in patients presenting with acute encephalopathy in the region.
A retrospective review of the data registry in Kuwait Medical Genetics Center for all cases diagnosed clinically and radiographically and confirmed genetically with BTBGD.
Twenty one cases from 13 different families were diagnosed with BTBGD in Kuwait. Most cases (86%) presented with confusion, dystonia, convulsions, or dysarthria, while three individuals were diagnosed pre-symptomatically during familial targeted genetic screening. Symptoms resolved completely within 2-week of treatment in two-thirds of the symptomatic cases but progressed in six of them to a variety of severe symptoms including severe cogwheel rigidity, dystonia and quadriparesis due to delayed presentation and management. Neuroradiological findings of the symptomatic cases revealed bilateral central changes in the basal ganglia. Two novel homozygous missense SLC19A3 variants were detected in a Kuwaiti and a Jordanian individuals, in addition to the previously reported Saudi founder homozygous variant, c.1264A > G; p.(Thr422Ala) in the remaining cases. Age of diagnosis ranged from newborn to 32 years, with a median age of 2-3 years. All cases are still alive receiving high doses of biotin and thiamine.
This is the first study reporting the phenotypic and genotypic spectrum of 21 individuals with BTBGD in Kuwait and describing two novel SLC19A3 variants. BTBGD is a treatable neurometabolic disease that requires early recognition and treatment initiation. This study highlights the importance of performing targeted molecular testing of the founder variant in patients presenting with acute encephalopathy in the region.
摘要：
背景：生物素-硫胺素反应性基底节病（BTBGD）是一种罕见的常染色体隐性遗传神经代谢疾病，由双等位基因致病性SLC19A3变异体引起，其特征是与意识错乱相关的亚急性脑病，抽搐,吞咽困难,构音障碍,或其他神经系统表现。
方法：对科威特医学遗传学中心的数据注册进行回顾性审查，对所有临床和影像学诊断并经BTBGD遗传证实的病例进行回顾性审查。
结果：来自13个不同家庭的21例患者在科威特被诊断为BTBGD。大多数病例（86％）表现为混乱，肌张力障碍,抽搐,或者构音障碍,而3名患者在家族性靶向遗传筛查中被诊断为预症状。在三分之二的有症状病例中，症状在治疗后2周内完全缓解，但其中6例进展为各种严重症状，包括严重的齿轮僵硬，由于延迟的表现和管理导致的肌张力障碍和四肢轻瘫。有症状病例的神经放射学发现显示基底神经节的双侧中央变化。在科威特和约旦个体中检测到两个新的纯合错义SLC19A3变体，除了先前报道的沙特创始人纯合变体，c.1264A>G;p.(Thr422Ala)在其余病例中。诊断年龄从新生儿到32岁，年龄中位数为2-3岁。所有病例接受高剂量的生物素和硫胺素仍然存活。
结论：这是第一项研究报告了科威特21名BTBGD患者的表型和基因型谱，并描述了两种新的SLC19A3变体。BTBGD是一种可治疗的神经代谢疾病，需要早期识别和开始治疗。这项研究强调了在该地区出现急性脑病的患者中对创始人变体进行靶向分子检测的重要性。
方法：对科威特医学遗传学中心的数据注册进行回顾性审查，对所有临床和影像学诊断并经BTBGD遗传证实的病例进行回顾性审查。
结果：来自13个不同家庭的21例患者在科威特被诊断为BTBGD。大多数病例（86％）表现为混乱，肌张力障碍,抽搐,或者构音障碍,而3名患者在家族性靶向遗传筛查中被诊断为预症状。在三分之二的有症状病例中，症状在治疗后2周内完全缓解，但其中6例进展为各种严重症状，包括严重的齿轮僵硬，由于延迟的表现和管理导致的肌张力障碍和四肢轻瘫。有症状病例的神经放射学发现显示基底神经节的双侧中央变化。在科威特和约旦个体中检测到两个新的纯合错义SLC19A3变体，除了先前报道的沙特创始人纯合变体，c.1264A>G;p.(Thr422Ala)在其余病例中。诊断年龄从新生儿到32岁，年龄中位数为2-3岁。所有病例接受高剂量的生物素和硫胺素仍然存活。
结论：这是第一项研究报告了科威特21名BTBGD患者的表型和基因型谱，并描述了两种新的SLC19A3变体。BTBGD是一种可治疗的神经代谢疾病，需要早期识别和开始治疗。这项研究强调了在该地区出现急性脑病的患者中对创始人变体进行靶向分子检测的重要性。
