title: A homozygote for the c.459+1G>A mutation in the ARSA gene presents with cerebellar ataxia as the only first clinical sign of metachromatic leukodystrophy.
abstract: Metachromatic leukodystrophy (MLD) is a rare lysosomal disorder caused by deficient activity of arylsulfatase A or the lack of saposin B, which results in the accumulation of sulfatide in the oligodendrocytes and in the Schwann cells. Three main clinical types of MLD can be distinguished according to the age of onset and the dynamics of clinical outcome: late infantile, juvenile, and adult. We report on a case of late infantile MLD presenting with cerebellar ataxia as the only first clinical sign preceding even changes in white matter visible in MR imaging. The diagnosis was made on the basis of successive MRI, characteristic of demyelination, which developed in the course of the disease, and on the results of the following biochemical and molecular analyses. Very low residual activity of arylsulfatase A was demonstrated in blood leukocytes and the patient was a homozygote for a common mutation c.459+1G>A in the ARSA gene. Since cerebellar ataxia is a relatively common but unspecific neurological symptom in toddlers, it is recommended that MLD be considered as part of the differential diagnosis even if the initial neuroimaging studies are normal and ataxia is the only clinical symptom of the disease.
authors.affiliation: Institute of Psychiatry and Neurology, Department of Genetics, Warsaw, Poland. Electronic address: alugipin@yahoo.com.
authors.forename: Agnieszka
authors.initials: A
authors.lastname: Lugowska
authors.affiliation: Institute of Mother and Child, Clinic of Neurology of Child and Adolescents, Warsaw, Poland.
authors.forename: Hanna
authors.initials: H
authors.lastname: Mierzewska
authors.affiliation: Institute of Mother and Child, Department of Diagnostic Imaging, Warsaw, Poland.
authors.forename: Monika
authors.initials: M
authors.lastname: Bekiesińska-Figatowska
authors.affiliation: Institute of Mother and Child, Clinic of Neurology of Child and Adolescents, Warsaw, Poland.
authors.forename: Elżbieta
authors.initials: E
authors.lastname: Szczepanik
authors.affiliation: Institute of Mother and Child, Clinic of Neurology of Child and Adolescents, Warsaw, Poland.
authors.forename: Alicja
authors.initials: A
authors.lastname: Goszczańska-Ciuchta
authors.affiliation: Institute of Psychiatry and Neurology, Department of Genetics, Warsaw, Poland.
authors.forename: Małgorzata
authors.initials: M
authors.lastname: Bednarska-Makaruk
mesh_terms: D002524:Cerebellar Ataxia / Q000175:diagnosis* / Q000235:genetics*; D002553:Cerebroside-Sulfatase / Q000235:genetics*; D006720:Homozygote; D006801:Humans; D007223:Infant; D007966:Leukodystrophy, Metachromatic / Q000503:physiopathology*; D008279:Magnetic Resonance Imaging; D008297:Male; D009154:Mutation / Q000235:genetics*
chemical_list: D002553:Cerebroside-Sulfatase
keywords: Arylsulfatase A; Cerebellar ataxia; Lysosomal storage disease; Magnetic resonance imaging; Metachromatic leukodystrophy; Neurometabolic disease