Leukoencephalopathy with Brain Stem and Spinal Cord Involvement and Lactate Elevation - Study of the phenotype and genotype and their correlation

s ingediend voor het Amsterdam Kindersymposium 2013 47 Leukoencephalopathy with Brain Stem and Spinal Cord Involvement and Lactate Elevation Study of the phenotype and genotype and their correlation Eline M. Hamilton (1), Laura van Berge (1), Marjan E. Steenweg (1), Gert C. Scheper (1), Truus E. Abbink (1), Tarja Linnankivi (2), Marjo S. van der Knaap (1) (1) Department of Child Neurology, VU University medical center, Amsterdam (2) Department of Pediatric Neurology, Helsinki University Central Hospital, Helsinki, Finland INTRODUCTION Leukoencephalopathy with Brain Stem and Spinal Cord Involvement and Lactate Elevation (LBSL) is a rare autosomal recessive disorder with a distinctive MRI and spectroscopy pattern, clinically characterized by slowly progressive ataxia, spasticity and dorsal column dysfunction. The disease is caused by mutations in the DARS2 gene. There is a wide clinical variation. The aim of this study was to make an inventory of the clinical severity, disease course and genotype in LBSL patients and to study the possible infl uence of the genotype on the phenotype. METHODS A cross sectional observational study in 73 patients (64 families) with two proven DARS2 mutations was conducted. Clinical information was collected through questionnaires for physicians and families. RESULTS The clinical course in LBSL patients varied from neonatal onset, rapidly fatal disease up to an adult onset, mild disorder. The most common phenotype was characterized by childhood onset, slowly progressive neurological deterioration and normal intelligence. Apart from exceptional, severe cases, full wheelchair dependency was rare and predominantly occurred in adulthood. All patients were compound heterozygous and 44 diff erent DARS2 mutations were observed; 18 were novel. Almost all patients had at least one splice-site mutation. With this heterogeneity of genotypes, no genotype-phenotype correlation could be demonstrated. CONCLUSION This study describes the natural course and genotype in the largest cohort of LBSL patients to date. LBSL is a very heterogeneous disorder caused by numerous diff erent mutations. Larger groups of patients are required to study the genotype-phenotype correlation.