Amer Aya, Murrell Kathryn, Edmonds Liza, Bernhardt Isaac, Akroyd Rhonda, Ryder Bryony, Wilson Callum, Glamuzina Emma
Dunedin Hospital Te Whatu Ora Health New Zealand, Southern Dunedin New Zealand.
Adult and Paediatric National Metabolic Service Starship Children's Hospital, Te Toka Tumai, Te Whatu Ora Health New Zealand Tāmaki Makaurau Auckland New Zealand.
JIMD Rep. 2025 Jan 16;66(1):e12461. doi: 10.1002/jmd2.12461. eCollection 2025 Jan.
Deficiency of the Glut1 transporter due to mono-allelic variants in causes hypoglycorrhachia, resulting in a neurological spectrum from neonatal epilepsy to adult-onset paroxysmal movement disorders (PMD). The brain utilises ketone bodies as an alternative energy source to glucose. Thus, early initiation of the ketogenic diet (KD) is standard care for Glut1 deficiency syndrome (Glut1DS). Commencement and adherence in older Glut1DS patients is difficult to achieve, leaving few treatment options. Oral D,L-3-hydroxybutyrate (D,L-3-HB) crosses the blood-brain barrier, making it a potential treatment for Glut1DS.
A retrospective case review of patients with Glut1DS under the Adult and Paediatric National Metabolic Service (APNMS) of New Zealand, treated with D,L-3-HB between 2012 and 2023 was performed. Clinical notes, standardised, neuropsychological assessments and subjective data on and off D,L-3-HB were obtained. The best on and off D,L-3-HB measures of working memory (WMI) and processing speed (PSI) were compared to assess the efficacy.
D,L-3-HB was offered to 12 patients with Glut1DS (age 10-52 years). Compliance-dependent improvements in subjective, cognitive and adaptive function were reported by those who were reassessed on-treatment (9/12). Four reported improved PMD. Objective improvements were found in WM (9/9) and PS (6/9). Subjective improvements were reported in patients' health, wellbeing and independence.
KD remains standard of care for Glut1DS, but effective alternatives are lacking for those who do not tolerate this. D,L-3-HB was associated with improved WM, PS and perceived life quality in this small group of patients with Glut1DS, thus providing a potential treatment for this distinct group.
由于SLC2A1基因单等位基因突变导致葡萄糖转运蛋白1（Glut1）转运体缺乏，会引起脑脊液低糖，从而导致从新生儿癫痫到成人发作性运动障碍（PMD）的一系列神经症状。大脑利用酮体作为葡萄糖的替代能源。因此，早期开始生酮饮食（KD）是葡萄糖转运蛋白1缺乏综合征（Glut1DS）的标准治疗方法。对于年龄较大的Glut1DS患者，很难开始并坚持生酮饮食，治疗选择有限。口服D，L-3-羟基丁酸（D，L-3-HB）可穿过血脑屏障，使其成为治疗Glut1DS的潜在药物。
对2012年至2023年期间在新西兰成人及儿童国家代谢服务中心（APNMS）接受D，L-3-HB治疗的Glut1DS患者进行回顾性病例分析。获取了患者服用D，L-3-HB前后的临床记录、标准化神经心理学评估和主观数据。比较了服用D，L-3-HB前后工作记忆（WMI）和处理速度（PSI）的最佳测量值，以评估疗效。
12例Glut1DS患者（年龄10 - 52岁）接受了D，L-3-HB治疗。接受重新评估的患者（9/12）报告了主观、认知和适应功能方面依从性相关的改善。4例报告PMD有所改善。在工作记忆（9/9）和处理速度（6/9）方面发现了客观改善。患者在健康、幸福感和独立性方面有主观改善。
生酮饮食仍然是GlutlDS的标准治疗方法，但对于不耐受的患者缺乏有效的替代方案。在这一小群Glut1DS患者中，D，L-3-HB与工作记忆、处理速度的改善以及生活质量的提升相关，因此为这一特殊群体提供了一种潜在的治疗方法。
