Division of Metabolism, Department of Pediatric Subspecialties, Ospedale Pediatrico Bambino Gesù, IRCSS, Piazza S. Onofrio 4, 00165, Rome, Italy.
Psychology Clinic Unit, Department of Neuroscience, Ospedale Pediatrico Bambino Gesù, IRCCS, Piazza S. Onofrio 4, 00165, Rome, Italy.
Orphanet J Rare Dis. 2021 Oct 11;16(1):424. doi: 10.1186/s13023-021-02045-3.
Hyperinsulinemic hypoglycemia (HI) is the most frequent cause of recurrent hypoglycemia in children. Despite diagnostic and therapeutic advances, it remains an important cause of morbidity, leading to neurological complications, such as psychomotor retardation and epilepsy. Patients with diffuse drug-unresponsive HI manifest neurological impairment and neurobehavioral problems, even though surgically treated with a near-total pancreatectomy. Based on the analogies between HI and GLUT1 deficiency, both presenting with neuroglycopenia and lack of alternative cerebral energy sources, we administered a ketogenic diet (KD) in three drug-unresponsive GCK-HI patients with the aim of preserving neurodevelopment and avoiding the need of a near-total pancreatectomy. They presented recurrent symptomatic hypoglycemia, intellectual disability and refractory epilepsy. Patients were treated with classical KD for 79, 27 and 18 months, respectively.
All patients became asymptomatic in a few days and showed an important improvement of the alert state. Epilepsy disappeared and no appearance of novel hypoglycemic lesions was detected with a brain MRI. Cognitive and adaptive abilities rapidly improved and normalized. IQ rose significantly from 81 to 111 (p = 0.04) in patient 1, from 82 vs 95 (p = 0.04) in patient 2, from 60 to 90 (p = 0.04) in patient 3.
We demonstrated the safety and efficacy of KD in the treatment of drug-unresponsive GCK-HI at a short and long-term. The neuroprotective effects of KD determined the recovery from epilepsy and intellectual disabilities and averted the need of a near-total pancreatectomy. All patients and their families reported an improvement of physical and psychosocial well-being, with a substantial improvement of their quality of life. These results might change the course and the quality of life of these patients and their families, having a relevant impact on human lives. Therefore, KD might be considered the elective treatment in unresponsive forms of GCK-HI.
高胰岛素血症性低血糖（HI）是儿童反复发生低血糖的最常见原因。尽管在诊断和治疗方面取得了进展，但它仍然是发病率的一个重要原因，导致神经系统并发症，如精神运动发育迟缓和癫痫。弥漫性药物无反应性 HI 患者表现出神经功能障碍和神经行为问题，即使通过全胰切除术进行手术治疗。基于 HI 和 GLUT1 缺乏症之间的相似性，两者都表现为神经低血糖和缺乏替代的大脑能量来源，我们在 3 例药物无反应性 GCK-HI 患者中使用生酮饮食（KD），旨在保护神经发育并避免全胰切除术的需要。他们表现为反复出现症状性低血糖、智力障碍和难治性癫痫。患者分别接受了 79、27 和 18 个月的经典 KD 治疗。
所有患者在几天内无症状，并表现出警觉状态的重要改善。癫痫消失，脑部 MRI 未发现新的低血糖病变。认知和适应能力迅速改善并恢复正常。智商在患者 1 中从 81 显著升高至 111（p=0.04），在患者 2 中从 82 升至 95（p=0.04），在患者 3 中从 60 升至 90（p=0.04）。
我们证明了 KD 在治疗药物无反应性 GCK-HI 中的短期和长期安全性和有效性。KD 的神经保护作用决定了癫痫和智力障碍的恢复，并避免了全胰切除术的需要。所有患者及其家属报告身体和社会心理幸福感的改善，生活质量有了实质性提高。这些结果可能改变这些患者及其家属的病程和生活质量，对人类生活产生重大影响。因此，KD 可能被视为无反应性 GCK-HI 的首选治疗方法。
