Unspecific white matter hyperintensity in T2-weighted imaging and dystonia as the first manifestations of ataxia telangiectasia

Abstract

Objective: Ataxia telangiectasia (AT) is an autosomal recessive genomic instability syndrome characterized by cerebellar ataxia, immunodeficiency and cancer predisposition. Neurodegeneration in AT is closely associated with the absence or partial lack of the ataxia telangiectasia-mutated (ATM) kinase. ATM is a central player in maintaining cellular homeostasis. Magnetic resonance imaging (MRI) studies are usually without pathology in early infancy; in childhood, cerebellar atrophy and, in the second decade of life, hyperintensive lesions in the white matter occur. We present the first case in a toddler of genetically confirmed AT which mimics a leucencephalopathy. Methods: The diagnostic work-up was demonstrated and the clinical phenotype was described in 1 male patient with genetically confirmed AT. A salient neurological history including a video documentation of the treatment progress was obtained. Results: Patient presented firstly in our hospital at 18 months of age while walking, standing and sitting without support was not possible due to severe trunk dystonia and axillar muscular hypotonia. First symptom was recognized at 11 months of age with unstable sitting. MRI study showed white matter hyperintensity periventricular and parietal in T2-weighted imaging. Alpha-fetoprotein was 26.3 IU/L (<10), IgG and IgA were decreased. Two newly described heterozygote mutations were found in the ATM-gene. To ensure the diagnosis, ATM kinase activity and ATM protein levels were measured, showing the absence of detectable ATM protein and absence of ATM kinase activity. Therapy with carbidopa- levodopa was initiated twelve months ago with a maximum of 5 mg/kg per day; gait and up-right standing clearly improved under medication. Conclusion: In AT patients white matter lesions without cerebellar atrophy can occur early in childhood. Dystonia could be the first movement disturbance in AT. In atypical cases the diagnosis should be confirmed by measurements of ATM kinase activity and ATM protein levels.