Medizinische Universität Graz Austria/Österreich - Forschungsportal - Medical University of Graz
Gewählte Publikation:
SHR Neuro Krebs Kardio Lipid Stoffw Microb
Kumperscak, HG; Plesnicar, BK; Zalar, B; Gradisnik, P; Seruga, T; Paschke, E.
Adult metachromatic leukodystrophy: a new mutation in the schizophrenia-like phenotype with early neurological signs.
Psychiatr Genet. 2007; 17(2):85-91
Doi: 10.1097/YPG.0b013e3280298280
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- Co-Autor*innen der Med Uni Graz
- Paschke Eduard
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- Abstract:
- OBJECTIVES: The adult type of metachromatic leukodystrophy can manifest itself as motor or as psycho-cognitive form, the latter is very similar to schizophrenia. We report on two sisters with adult metachromatic leukodystrophy who display symptoms of both forms. METHODS: Presented are genotype analyses and 4-year follow-up data regarding clinical manifestations as well as neurocognitive and neuroimaging results for two adult sisters with metachromatic leukodystrophy. RESULTS: Whereas the younger sister developed disorganized schizophrenia-like symptoms, the other exhibited schizophrenia-like, negative symptoms. In both sisters, neurological signs were already present at the onset of the disease and progression towards dementia was documented within 1-2 years. In peripheral leukocytes, the activity of arylsulphatase A was reduced to 2 and 5% of the mean normal activity in both women. Genotype analysis revealed compound heterozygosity for a known severe splice site mutation, (c.459+1G>A) together with two known polymorphisms, [(c.937G>T), (p.Trp193Asp)] and [(c.1530C>G), (p.Thr391Ser)], and a novel missense mutation, (c.1194C>T). The latter results in the exchange of a conserved polar amino acid, threonine 279, to hydrophobic isoleucine (Thr279Ileu), which could not be found among >100 control alleles. A family analysis identified T279I as the paternal allele, whereas (c.459+1G>A) as well as the two polymorphisms were inherited from the mother. This is consistent with a disease-causing effect of the novel mutation. CONCLUSIONS: The novel mutation, T279I detected in our patients, correlates with a specific phenotype with schizophrenia-like symptoms, neurological signs and cognitive impairment early in the course of the disease and a relatively fast progression towards dementia. This is in contrast to previous reports on adult metachromatic leukodystrophy patients with the psycho-cognitive phenotype who did not show any neurological signs for decades, however, most of these patients were heterozygous for another specific missense mutation, I179S.
- Find related publications in this database (using NLM MeSH Indexing)
- Adult -
- Age of Onset -
- Alternative Splicing -
- Cerebroside-Sulfatase - blood
- DNA Primers - blood
- Dementia - genetics
- Disease Progression - genetics
- Female - genetics
- Follow-Up Studies - genetics
- Humans - genetics
- Leukocytes - enzymology
- Leukodystrophy, Metachromatic - genetics
- Male - genetics
- Mutation - genetics
- Pedigree - genetics
- Phenotype - genetics
- Polymorphism, Single Nucleotide - genetics
- Schizophrenia - genetics
- Siblings - genetics
- Find related publications in this database (Keywords)
- arylsulphatases
- metachromatic leukodystrophy
- mutation
- psycho-cognitive type
- schizophrenia