Author/Editor		Gregorič Kumperščak, Hojka; Kores-Plesničar, Blanka; Zalar, Bojan; Gradišnik, Peter; Šeruga, Tomaž; Paschke, Eduard
Title		Adult metachromatic leukodystrophy: a new mutation in the schizophrenia-like phenotype with early neurological signs
Type		članek
Source		Psychiatr Genet
Vol. and No.		Letnik 17, št. 2
Publication year		2007
Volume		str. 85-91
Language		eng
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. (Abstract truncated at 2000 characters)
Descriptors		LEUKODYSTROPHY, METACHROMATIC SCHIZOPHRENIA, DISORGANIZED INTELLIGENCE TESTS NEUROLOGIC MANIFESTATIONS DEPRESSION ALLELES ARYLSULFATASES POLYMERASE CHAIN REACTION MUTATION DEMYELINATING DISEASES