Motor and psycho-cognitive clinical types in adult metachromatic leukodystrophy: genotype/phenotype relationships?
Motor and psycho-cognitive clinical types in adult metachromatic leukodystrophy: genotype/phenotype relationships?
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DOI：
10.1016/s0928-4257(02)00019-0
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发表时间：
2002-04-01
影响因子：
--
通讯作者：
Colsch, B
中科院分区：
文献类型：
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作者：
Baumann, N;Turpin, JC;Colsch, B
异染性脑白质营养不良（MLD）是一种隐性常染色体疾病，其生化特征为主要在少突胶质细胞和巨噬细胞/小胶质细胞中积累硫代半乳糖苷脂（磺基半乳糖神经酰胺）。缺乏的酶是一种溶酶体水解酶，即芳基硫酸酯酶A。MLD是一种髓鞘形成障碍和脱髓鞘疾病。主要的临床形式是婴儿或青少年，但有些形式出现在成年期。这种疾病还涉及神经元细胞，因为硫苷脂也存在于神经元中，其中也发生降解缺陷。我们研究了12例成人MLD，明确区分了两种临床形式。其中1例主要表现为中枢神经系统运动体征（锥体、小脑和罕见肌张力障碍）和周围神经病变。另一种形式总是从行为异常开始，伴随着情绪的改变，特殊的社会反应;也发生了进行性的精神恶化。精神分裂症的诊断经常被提及。这些患者中的大多数人多年来没有任何神经系统症状，只有在出现神经系统症状或进行磁共振成像（MRI）时才能做出诊断。MRI显示弥漫性脱髓鞘，双侧且通常对称，可能暂时局限于脑室周围区域。成人MLD的诊断是生化的，证明芳基硫酸酯酶A（阿萨）和硫苷脂积累的活性低。为了确定神经元和神经胶质细胞在运动形式和心理认知形式的生理病理学中的各自参与，我们的第一种方法是根据临床状态寻找不同的突变。运动形式涉及纯合子形式的主要成人阿萨突变P426 L，而心理认知形式涉及作为复合杂合子的特定I179 S突变。(C)2002爱思唯尔科技有限公司版权所有。
Metachromatic leukodystrophy (MLD) is a recessive autosomal disease which is biochemically characterized by an accumulation of sulfatides (sulfogalactosylceramides) mainly in oligodendrocytes and macrophages/microglia. The deficient enzyme is a lysosomal hydrolase, cerebroside sulfate sulfatase (arylsulfatase A). MLD is both a dysmyelinating and a demyelinating disease. The main clinical forms are infantile or juvenile, but some forms appear at adulthood. This disease involves also neuronal cells as sulfatides are also present in neurons in which the defect in degradation occurs also. We have studied 12 cases of adult MLD and clearly distinguished two clinical forms. One of them was characterized by mainly central nervous system motor signs (pyramidal, cerebellar, and seldom dystonia) and a peripheral neuropathy. The other form always started by behavioural abnormalities with modifications of mood, peculiar social reactions; a progressive mental deterioration occurred also. The diagnosis of schizophrenia was often mentioned. Most of these patients remained for many years without any neurological symptoms, and the diagnosis was only made when neurological signs appeared, or when Magnetic Resonance Imaging (MRI) was performed. MRI showed a diffuse demyelination, bilateral and often symmetrical, which could be temporarily limited to the periventricular areas. The diagnosis of adult MLD was biochemical, evidencing the low activity of arylsulfatase A (ASA) and sulfatide accumulation. To determine the respective participation of neurons and glial cells in the physiopathology of both the motor forms and the psycho-cognitive forms, our first approach was to search for mutations differing according to the clinical status. Motor forms involved the major adult ASA mutation P426L in a homozygote form in contrast to psycho-cognitive forms which involved as a compound heterozygote a specific I179S mutation. (C) 2002 Elsevier Science Ltd. All rights reserved.