Motor and psycho-cognitive clinical types in adult metachromatic leukodystrophy: genotype/phenotype relationships?

被引:37
作者
Baumann, N [1 ]
Turpin, JC [1 ]
Lefevre, M [1 ]
Colsch, B [1 ]
机构
[1] Hop La Pitie Salpetriere, INSERM, Unit 495, Neurochem Lab, Paris, France
关键词
metachromatic leukodystrophy; sulfatides; psychosis; cellular interactions; arylsulfatase A;
D O I
10.1016/S0928-4257(02)00019-0
中图分类号
Q189 [神经科学];
学科分类号
071006 ;
摘要
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.
引用
收藏
页码:301 / 306
页数:6
相关论文
共 40 条
[1]   THE 1ST ALZHEIMER-DISEASE CASE - A METACHROMATIC LEUKODYSTROPHY [J].
AMADUCCI, L ;
SORBI, S ;
PIACENTINI, S ;
BICK, KL .
DEVELOPMENTAL NEUROSCIENCE, 1991, 13 (4-5) :186-187
[2]   METACHROMATIC FORM OF DIFFUSE CEREBRAL SCLEROSIS .6. A RAPID TEST FOR SULFATASE A DEFICIENCY IN METACHROMATIC LEUKODYSTROPHY (MLD) URINE [J].
AUSTIN, J ;
ARMSTRONG, D ;
SHEARER, L ;
MCAFEE, D .
ARCHIVES OF NEUROLOGY, 1966, 14 (03) :259-+
[3]  
BAUMANN A, 2002, ENCYCL MED CHIR, P37
[4]   ADULT FORMS OF METACHROMATIC LEUKODYSTROPHY - CLINICAL AND BIOCHEMICAL APPROACH [J].
BAUMANN, N ;
MASSON, M ;
CARREAU, V ;
LEFEVRE, M ;
HERSCHKOWITZ, N ;
TURPIN, JC .
DEVELOPMENTAL NEUROSCIENCE, 1991, 13 (4-5) :211-215
[5]   Biology of oligodendrocyte and myelin in the mammalian central nervous system [J].
Baumann, N ;
Pham-Dinh, D .
PHYSIOLOGICAL REVIEWS, 2001, 81 (02) :871-927
[6]  
BAUMANN N, 1998, EUR M GLIAL CELL FUN
[7]   Evidence for activation of microglia in patients with psychiatric illnesses [J].
Bayer, TA ;
Buslei, R ;
Havas, L ;
Falkai, P .
NEUROSCIENCE LETTERS, 1999, 271 (02) :126-128
[8]   SIMULTANEOUS DETECTION OF THE 2 MOST FREQUENT METACHROMATIC LEUKODYSTROPHY MUTATIONS [J].
BERGER, J ;
MOLZER, B ;
GIESELMANN, V ;
BERNHEIMER, H .
HUMAN GENETICS, 1993, 92 (04) :421-423
[9]  
Brault JL, 1997, REV NEUROL-FRANCE, V153, P193
[10]   GLIAL CELLS AND CENTRAL MYELIN SHEATH [J].
BUNGE, RP .
PHYSIOLOGICAL REVIEWS, 1968, 48 (01) :197-+