P 1077. Leukoencephalopathy with Brain Stem and Spinal Cord Involvement and Lactate Elevation (LBSL): A Case Report

Background: Leukoencephalopathy with brain stem and spinal cord involvement and lactate elevation (LBSL) caused by a mutation in DARS2 gene (Chr. 1q25.1) which encodes for mitochondrial aspartyl-tRNA synthetase is a rare differential diagnosis in patients with leukoencephalopathy. LBSL includes affection of cerebellum, pyramidal tracts, and posterior column of spinal cord. The phenotype is characterized by progressive ataxia, spasticity, disturbed sense of position, and vibration sensation, as well as progressive loss of cognitive functions, dysarthria, and epilepsy. We report about clinical presentation and longer term outcome in a 9-year-old boy with mild developmental delay in gross and fine motor skills with a mutation in DARS2 gene.

Case Report: A 6-year-old boy, the first child of nonconsanguineous parents, was presented for further evaluation of developmental delay and learning deficits. From the age of 6 years, he developed a delay of gross motor and fine motor skills and also graphomotor skills. Language development was appropriate for age. Standardized psychological testing (HAWIK-IV) confirmed normal mental development but deficits in common understanding and processing speed. Head circumference was normal (62. perc.). There were no signs of clinical or electrographic seizure activity. Ophthalmological findings were normal. Cranial MRI at the age of 6 years showed diffuse T2w hyperintense, T1w hypointense signal alterations of the supra- and infratentorial white matter. Lysosomal and peroxisomal diseases including Alexander’s disease could be excluded. Serum and cerebrospinal fluid lactate concentrations were normal. Microarray analysis for specific anomalies showed a DARS2 mutation. During the further course of 2 years, the boy showed clinically stable symptoms including age-appropriate cognitive ability (HAWIK-IV).

Conclusion: In the presence of clinically shown mild developmental disorder and characteristic brain imaging findings of leukoencephalopathy with selective involvement of specific long white matter tracts in brain stem and spinal cord, a mutation in DARS2 gene and LBSL should be included in the differential diagnosis. Lactate peak is detectable by MR spectroscopy. Contrary to previously described rapidly progressive spasticity and ataxia, our patient showed a stable course including age-appropriate cognitive ability (HAWIK-IV) up to an observation period of 2 years.