Stoeck Katharina, Psychogios Marios Nikos, Ohlenbusch Andreas, Steinfeld Robert, Schmidt Jens
Department of Neurology, University Medical Center Göttingen, Germany.
Department of Neuroradiology, University Medical Center Göttingen, Germany.
J Alzheimers Dis. 2016;51(3):683-7. doi: 10.3233/JAD-150819.
A 48-year-old male patient presented with personality changes and progressive memory loss over 2 years with initially suspected Hashimoto's encephalopathy. Strategy of diagnostic workup of early onset dementia included dementia from neurodegenerative, neuroinflammatory, metabolic/toxic, and psychiatric origin. The patient's neurological exam was normal. MRI revealed a leukencephalopathy, predominantly in the frontal periventricular white matter, without notable changes over 2 years. On neurophysiological examination, prolonged central conduction times and a sensorimotor polyneuropathy were noted. Neuropsychological impairment included disorientation in place and a reduced short time memory. Behavioral alterations were predominated by sudden mood changes and disinhibition. Cerebrospinal fluid was normal. Despite presence of thyroid autoantibodies, glucocorticosteroid treatment did not improve the dementia. A metachromatic leukodystrophy was diagnosed by decreased arylsulfatase-A activity in leucocytes/fibroblasts and identification of a compound heterozygous mutation in the ARSA gene: c.542T>G (exon 3) and the novel mutation c.1013T>C (exon 6). Pathogenic function was suggested by bioinformatic mutation search. In a patient with early onset dementia, strategic diagnostic workup including genetic assessment revealed an adult-onset metachromatic leukodystrophy with a novel mutation in the arylsulfatase A gene.
一名48岁男性患者出现人格改变和进行性记忆力减退2年，最初怀疑为桥本脑病。早发性痴呆的诊断检查策略包括神经退行性、神经炎症性、代谢/中毒性和精神性病因导致的痴呆。患者的神经系统检查正常。磁共振成像（MRI）显示白质脑病，主要位于额叶脑室周围白质，2年内无明显变化。神经生理学检查发现中枢传导时间延长和感觉运动性多发性神经病。神经心理学损害包括地点定向障碍和短时记忆减退。行为改变主要表现为突然情绪变化和去抑制。脑脊液正常。尽管存在甲状腺自身抗体，但糖皮质激素治疗并未改善痴呆症状。通过白细胞/成纤维细胞中芳基硫酸酯酶A活性降低以及在ARSA基因中鉴定出复合杂合突变：c.542T>G（外显子3）和新突变c.1013T>C（外显子6），诊断为异染性脑白质营养不良。生物信息学突变搜索提示了致病功能。在一名早发性痴呆患者中，包括基因评估在内的策略性诊断检查发现了成人型异染性脑白质营养不良，其芳基硫酸酯酶A基因存在新突变。
