Gautschi Matthias, Weisstanner Christian, Slotboom Johannes, Nava Esmeralda, Zürcher Theres, Nuoffer Jean-Marc
1] Department of Paediatrics, University Hospital Bern, Inselspital, Bern, Switzerland [2] Institute of Clinical Chemistry, University Hospital Bern, Inselspital, Bern, Switzerland.
Institute of Neuroradiology, University Hospital Bern, Inselspital, Bern, Switzerland.
Pediatr Res. 2015 Jan;77(1-1):91-8. doi: 10.1038/pr.2014.154. Epub 2014 Oct 7.
Multiple acyl-CoA dehydrogenase deficiency- (MADD-), also called glutaric aciduria type 2, associated leukodystrophy may be severe and progressive despite conventional treatment with protein- and fat-restricted diet, carnitine, riboflavin, and coenzyme Q10. Administration of ketone bodies was described as a promising adjunct, but has only been documented once.
We describe a Portuguese boy of consanguineous parents who developed progressive muscle weakness at 2.5 y of age, followed by severe metabolic decompensation with hypoglycaemia and coma triggered by a viral infection. Magnetic resonance (MR) imaging showed diffuse leukodystrophy. MADD was diagnosed by biochemical and molecular analyses. Clinical deterioration continued despite conventional treatment. Enteral sodium D,L-3-hydroxybutyrate (NaHB) was progressively introduced and maintained at 600 mg/kg BW/d (≈ 3% caloric need). Follow up was 3 y and included regular clinical examinations, biochemical studies, and imaging.
During follow up, the initial GMFC-MLD (motor function classification system, 0 = normal, 6 = maximum impairment) level of 5-6 gradually improved to 1 after 5 mo. Social functioning and quality of life recovered remarkably. We found considerable improvement of MR imaging and spectroscopy during follow up, with a certain lag behind clinical recovery. There was some persistent residual developmental delay.
NaHB is a highly effective and safe treatment that needs further controlled studies.
多种酰基辅酶A脱氢酶缺乏症（MADD），也称为2型戊二酸尿症，相关的脑白质营养不良可能很严重且呈进行性发展，尽管采用了蛋白质和脂肪限制饮食、肉碱、核黄素和辅酶Q10进行常规治疗。酮体给药被描述为一种有前景的辅助治疗方法，但仅有一次记录。
我们描述了一名葡萄牙男孩，其父母为近亲结婚，他在2.5岁时出现进行性肌肉无力，随后因病毒感染引发严重代谢失代偿，出现低血糖和昏迷。磁共振成像显示弥漫性脑白质营养不良。通过生化和分子分析诊断为MADD。尽管进行了常规治疗，临床病情仍继续恶化。逐渐引入肠内D，L-3-羟基丁酸钠（NaHB）并维持在600mg/kg体重/天（约占热量需求的3%）。随访3年，包括定期临床检查、生化研究和影像学检查。
随访期间，最初的GMFC-MLD（运动功能分类系统，0=正常，6=最大损伤）水平5-6在5个月后逐渐改善至1。社交功能和生活质量显著恢复。我们发现随访期间磁共振成像和波谱有相当大的改善，但在临床恢复方面有一定滞后。仍存在一些持续性的发育迟缓。
NaHB是一种高效且安全的治疗方法，需要进一步的对照研究。
