Del Rizzo Monica, Galderisi Alfonso, Celato Andrea, Furlan Francesca, Giordano Laura, Cazzorla Chiara, Fasan Ilaria, Moretti Carlo, Zschocke Johannes, Burlina Alberto B
Division of Metabolic Diseases, Department of Woman and Child Health, University Hospital of Padua, Padua, Italy.
Diabetology Unit, Department of Woman and Child Health, University Hospital of Padua, Padua, Italy.
Eur J Pediatr. 2016 Aug;175(8):1123-8. doi: 10.1007/s00431-016-2699-5. Epub 2016 Feb 5.
The coexistence of two diseases associated with different metabolic disorders is a very rare event. Some associations, although sporadic, can be particularly challenging both in terms of diagnostic and therapeutic management and in terms of theoretical perspective. Here, we report a child affected by type 1 diabetes mellitus (T1DM) and glutaric aciduria type 1 (GA1). The child was diagnosed with classical T1DM at 15 months of age, with a tendency toward hypoglycemia. A few months later, during an acute intercurrent infective episode, the child displayed acute hypotonia of the lower limbs and limbs dystonia. A brain MRI showed bilateral striatal necrosis, suggesting GA1 diagnosis. Treatment with a low-lysine dietary regimen and carnitine supplementation was started and resulted in an improvement in metabolic control and a reduction of hypoglycemic episodes along with an increasing in insulin daily dose. After 2 years, the neurological outcome consisted of a reduction in dystonic movements and a metabolic stability of both diseases.
This case provides some insight into the reciprocal interconnections between the two metabolic disorders. Similar pathogenic mechanisms responsible for the neuronal injury might have impacted each other, and a strict relationship between a specific aspect of GA1-impaired metabolism and glucose homeostasis might explain how the tailored management of GA1 was not only effective in controlling the disease, but it also resulted in an improvement in the control of the glycemic profile. What in known: • Glutaric aciduria type 1 (GA1) usually presents in childhood with severe and possibly irreversible neuronal damage, triggered by a catabolic stress • The association of GA1 with other diseases, including type 1 diabetes mellitus (T1DM), is a rare event, complicating the treatment management What is new: • Insulin treatment has a role in preventing GA1 metabolic decompensation, even in the catabolic condition of hypoglycemia • Promoting GA1 metabolic equilibrium by tailoring drug and dietary treatment in our patient affect by T1DM has a positive impact also in improving glycemic balance.
两种与不同代谢紊乱相关的疾病共存是非常罕见的情况。一些关联虽然是散发性的，但在诊断和治疗管理以及理论层面都可能极具挑战性。在此，我们报告一名患有1型糖尿病（T1DM）和1型戊二酸血症（GA1）的儿童。该儿童在15个月大时被诊断为典型的T1DM，有低血糖倾向。几个月后，在一次急性并发感染期间，该儿童出现下肢急性肌张力减退和肢体肌张力障碍。脑部磁共振成像（MRI）显示双侧纹状体坏死，提示GA1诊断。开始采用低赖氨酸饮食方案和补充肉碱进行治疗，结果代谢控制得到改善，低血糖发作减少，同时胰岛素每日剂量增加。2年后，神经学结果是肌张力障碍运动减少，两种疾病的代谢均保持稳定。
该病例为这两种代谢紊乱之间的相互联系提供了一些见解。导致神经元损伤的类似致病机制可能相互影响，GA1受损代谢的一个特定方面与葡萄糖稳态之间的紧密关系或许可以解释为何针对GA1的定制管理不仅能有效控制疾病，还能改善血糖状况的控制。已知情况：• 1型戊二酸血症（GA1）通常在儿童期出现，由分解代谢应激引发严重且可能不可逆的神经元损伤 • GA1与其他疾病（包括1型糖尿病（T1DM））的关联是罕见事件，使治疗管理复杂化 新发现：• 即使在低血糖的分解代谢状态下，胰岛素治疗在预防GA1代谢失代偿方面也有作用 • 通过为我们这位受T1DM影响的患者定制药物和饮食治疗来促进GA1代谢平衡，对改善血糖平衡也有积极影响。
