Müller vom Hagen J, Karle K N, Schüle R, Krägeloh-Mann I, Schöls L
Department of Neurodegenerative Diseases, Hertie-Institute for Clinical Brain Research, University of Tübingen, Tübingen, Germany; German Centre for Neurodegenerative Diseases (DZNE), Tübingen, Germany.
Eur J Neurol. 2014 Jul;21(7):983-8. doi: 10.1111/ene.12423. Epub 2014 Apr 2.
In chronic progressive spasticity of the legs many rare causes have to be considered, including leukodystrophies due to neurometabolic disorders. To determine the frequency of leukodystrophies and the phenotypic spectrum patients with cryptic spasticity of the legs were screened for underlying neurometabolic abnormalities.
Seventy-six index patients presenting with adult-onset lower limb spasticity of unknown cause consistent with autosomal recessive inheritance were included in this study. Screening included serum levels of very long chain fatty acids for X-linked adrenoleukodystrophy/adrenomyeloneuropathy and lysosomal enzyme activities in leukocytes for metachromatic leukodystrophy, GM1-gangliosidosis, Tay-Sachs, Sandhoff and Krabbe disease. If clinical evidence was indicative of other types of leukodystrophies, additional genetic testing was conducted. Clinical characterization included neurological and psychiatric features and magnetic resonance imaging.
Basic screening detected one index patient with metachromatic leukodystrophy, two patients with Krabbe disease and four patients with adrenoleukodystrophy/adrenomyeloneuropathy. Additional genetic testing revealed one patient with vanishing white matter disease. These patients accounted for an overall share of 11% of leukodystrophies. One patient with Krabbe disease and three patients with adrenoleukodystrophy/adrenomyeloneuropathy presented with pure spasticity of the lower limbs, whilst one patient each with Krabbe disease, metachromatic leukodystrophy and adrenoleukodystrophy/adrenomyeloneuropathy showed additional complicating symptoms.
Adult patients presenting with cryptic spasticity of the legs should be screened for underlying X-linked adrenoleukodystrophy/adrenomyeloneuropathy and lysosomal disorders, irrespective of the presence of additional complicating symptoms. Leukodystrophies may manifest as late as the sixth decade and hyperintensity of cerebral white matter on magnetic resonance FLAIR images is not obligatory.
在腿部慢性进行性痉挛中，必须考虑许多罕见病因，包括神经代谢紊乱所致的脑白质营养不良。为确定脑白质营养不良的发生率及表型谱，对隐匿性腿部痉挛患者进行潜在神经代谢异常筛查。
本研究纳入76例成年起病、病因不明、表现为下肢痉挛且符合常染色体隐性遗传的索引患者。筛查包括检测血清极长链脂肪酸水平以排查X连锁肾上腺脑白质营养不良/肾上腺脊髓神经病，检测白细胞溶酶体酶活性以排查异染性脑白质营养不良、GM1神经节苷脂贮积症、泰-萨克斯病、桑德霍夫病和克拉伯病。若临床证据提示为其他类型的脑白质营养不良，则进行额外的基因检测。临床特征包括神经和精神方面的表现以及磁共振成像。
基础筛查发现1例异染性脑白质营养不良索引患者、2例克拉伯病患者和4例肾上腺脑白质营养不良/肾上腺脊髓神经病患者。额外的基因检测发现1例伴脑白质消失症患者。这些患者占脑白质营养不良患者总数的11%。1例克拉伯病患者和3例肾上腺脑白质营养不良/肾上腺脊髓神经病患者仅表现为下肢单纯性痉挛，而1例克拉伯病患者、1例异染性脑白质营养不良患者和1例肾上腺脑白质营养不良/肾上腺脊髓神经病患者还伴有其他复杂症状。
对于成年隐匿性腿部痉挛患者，无论是否存在其他复杂症状，均应筛查潜在的X连锁肾上腺脑白质营养不良/肾上腺脊髓神经病和溶酶体疾病。脑白质营养不良可能直到第六个十年才出现，磁共振FLAIR图像上脑白质高信号并非必然出现。
