Late-onset metachromatic leukodystrophy: genotype strongly influences phenotype
| Autor: | Johannes Berger, Volkmar Gieselmann, Helmut Rauschka, Timothy M. Cox, S. Tardieu, Eric LeGuern, Fahmy Aboul-Enein, H. Bernheimer, Hugo W. Moser, Benoit Colsch, Bernard Zalc, Nicole Baumann, William Krivit, Ron A. Wevers, U. Reuner, M. Lefevre, Manfred Schmidbauer, C. Olivier, Ann B. Moser, J. C. Turpin, M. Krammer, Anna Tylki-Szymańska |
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| Rok vydání: | 2006 |
| Předmět: |
Adult
Male medicine.medical_specialty Arylsulfatase A Adolescent Genotype Proline Energy and redox metabolism [NCMLS 4] Neural Conduction Late onset Biology Neuroinformatics [DCN 3] Compound heterozygosity Statistics Nonparametric Central nervous system disease Degenerative disease Leucine Internal medicine medicine Perception and Action [DCN 1] Humans Isoleucine Child Cerebroside-Sulfatase Cerebellar ataxia Genetic heterogeneity Electroencephalography Leukodystrophy Metachromatic Glycostation disorders [IGMD 4] medicine.disease Magnetic Resonance Imaging Neuromuscular development and genetic disorders [UMCN 3.1] Metachromatic leukodystrophy Endocrinology Phenotype Genetic defects of metabolism [UMCN 5.1] Mutation Female Neurology (clinical) medicine.symptom |
| Zdroj: | Neurology, 67, 5, pp. 859-63 Neurology, 67, 859-63 |
| ISSN: | 0028-3878 |
| Popis: | Contains fulltext : 49461.pdf (Publisher’s version ) (Closed access) BACKGROUND: P426L and I179S are the two most frequent mutations in juvenile and adult metachromatic leukodystrophy (late-onset MLD), which, in contrast to infantile MLD, show marked phenotypic heterogeneity. OBJECTIVE: To search for genotype-phenotype correlations in late-onset MLD. METHODS: The authors reviewed the clinical course of 22 patients homozygous for mutation P426L vs 20 patients heterozygous for mutation I179S, in which the second arylsulfatase A (ASA) mutation had also been determined. RESULTS: P426L homozygotes principally presented with progressive gait disturbance caused by spastic paraparesis or cerebellar ataxia; mental disturbance was absent or insignificant at the onset of disease but became more apparent as the disease evolved. In contrast, compound heterozygotes for I179S presented with schizophrenia-like behavioral abnormalities, social dysfunction, and mental decline, but motor deficits were scarce. Reduced peripheral nerve conduction velocities and less residual ASA activity were present in P426L homozygotes vs I179S heterozygotes. CONCLUSION: The characteristic clinical differences between homozygous P426L and compound heterozygous I179S patients establish a distinct genotype-phenotype correlation in late-onset metachromatic leukodystrophy. |
| Databáze: | OpenAIRE |
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