www.neurologia.com Rev Neurol 2014; 58 (Congr 1): C1ͲC496 C84 Standardized description of rare diseases –the natural course and treatment of metachromatic leukodystrophy Samuel Groeschel, Christiane Kehrer, Ingeborg Krägeloh-Mann Department of Paediatric Neurology and Developmental Medicine. University Children’s Hospital. Tübingen, Germany. Corresponding author: Samuel Groeschel MD. Department of Paediatric Neurology and Developmental Medicine. University Children’s Hospital. Hoppe-Seyler-Strasse 1. 72076 Tübingen, Germany. Fax: +49 7071/295473. E-mail: Samuel.Groeschel@med.uni-tuebingen.de Summary. Metachromatic leukodystrophy (MLD) is a rare neurometabolic disorder leading to demyelination and rapid neurological deterioration. As therapeutic options evolve, it seems essential to understand and quantify progression of the natural disease. In an ongoing nationwide study, we therefore established and validated standardized assessment tools and objectively described motor and cognitive function in children with MLD. Furthermore, we were able to systematically characterize the cerebral changes associated with MLD non-invasively using MRI. Both a visual MRI scoring system as well as a quantification of the ‘demyelination load’ were established and applied in our large cohort. This allowed the identification of typical MRI changes in children with late-infantile and juvenile MLD and the quantification of demyelination and atrophy in the brain. These MRI parameters were correlated with the decline of neurological function in MLD underlining their potential as surrogate parameters for disease progression. In addition, the treatment effect of hematopoietic stem cell transplantation in children with late- infantile and juvenile MLD was evaluated and compared to the natural history data. In conclusion, the standardized description of the natural disease course of MLD is essential in increasing our knowledge about this rare disease and thereby improving patient counselling. In addition, these data may serve as reference data for the evaluation of therapeutic interventions. Introduction Metachromatic leukodystrophy (MLD) is a rare lysosomal storage disorder caused by a deficiency of the catabolic enzyme arylsulfatase A, resulting in accumulation of sulfatides [1]. Sulfatide is an important component of myelin in the (central and peripheral) nervous system and its accumulation causes progressive demyelination as a pathological feature of MLD, leading to various neurological symptoms [2]. Depending on the onset of first symptoms, three clinical forms of the disease have been identified. Children with the late-infantile form have their disease onset during the first years of life and undergo a rapid neurological deterioration with loss of motor function as a key feature. In patients with the juvenile form, onset of the disease is later and rate of progression clearly slower; in the adult form with an onset after the age of 16 years, cognitive and psychiatric symptoms may predominate and may precede motor and neurological symptoms [3]. Currently, new therapeutic approaches are emerging, including gene therapy and enzyme replacement therapy [4–8]. Outside of these trials, however, the only available treatment option is