Glucose transporter type 1 deficiency syndrome (GLUT-1DS) is characterized by alterations in glucose translocation through the blood–brain barrier (BBB) due to mutation involving the GLUT-1 transporter. The fundamental therapy is ketogenic diet (KD) that provide an alternative energetic substrate — ketone bodies that across the BBB via MCT-1 — for the brain. Symptoms are various and include intractable seizure, acquired microcephalia, abnormal ocular movement, movement disorder, and neurodevelopment delay secondary to an energetic crisis for persistent neuroglycopenia. KD is extremely effective in controlling epileptic seizures and has a positive impact on movement disorders and cognitive impairment. Cases of KD resistance are rare, and only a few of them are reported in the literature, all regarding seizure. Our study describes a peculiar case of GLUT-1DS due to a new deletion involving the first codon of SLC2A1 gene determining a loss of function with a resistance to KD admitted to hospital due to intractable episodes of dystonia. This patient presented a worsening of symptomatology at higher ketonemia values but without hyperketosis and showed a complete resolution of symptomatology while maintaining low ketonemia values. Our study proposes an in-silico genomic and proteomic analysis aimed at explaining the atypical response to KD exhibited by our patient. In this way, we propose a new clinical and research approach based on precision medicine and molecular modelling to be applied to patients with GLUT-1DS resistant to first-line treatment with ketogenic diet by in silico study of genetic and altered protein product.

1 型葡萄糖转运蛋白缺乏综合征 (GLUT-1DS) 的特点是由于涉及 GLUT-1 转运蛋白的突变导致葡萄糖通过血脑屏障 (BBB) 的转运发生改变。基本疗法是生酮饮食 (KD)，它为大脑提供另一种能量底物——通过 MCT-1 穿过 BBB 的酮体。症状多种多样，包括顽固性癫痫发作、获得性小头畸形、眼球运动异常、运动障碍以及继发于持续性神经低血糖症的能量危机的神经发育迟缓。生酮饮食对于控制癫痫发作非常有效，并对运动障碍和认知障碍具有积极影响。KD 耐药的病例很少见，文献中只报道了其中的少数病例，而且全部都与癫痫发作有关。我们的研究描述了 GLUT-1DS 的一个特殊病例，该病例是由于SLC2A1基因的第一个密码子的新缺失决定了功能丧失，并对 KD 具有抵抗力，因顽固性肌张力障碍而入院。该患者在较高的酮血症值下表现出症状恶化，但没有酮症过多，并且在维持低酮血症值的同时表现出症状完全缓解。我们的研究提出了一种计算机基因组和蛋白质组分析，旨在解释我们的患者对川崎病表现出的非典型反应。通过这种方式，我们提出了一种基于精准医学和分子模型的新临床和研究方法，通过对遗传和改变的蛋白质产物进行计算机研究，将其应用于对生酮饮食一线治疗耐药的 GLUT-1DS 患者。