Leukoencephalopathy with brain stem and spinal cord involvement-high lactate syndrome

Leukoencephalopathy with brain stem and spinal cord involvement and lactate elevation (LBSL) is a rare inherited neurological disorder caused by mutations in the DARS2 gene, which encodes mitochondrial aspartyl-tRNA synthetase. This enzyme is essential for mitochondrial protein synthesis, and its dysfunction leads to impaired energy metabolism in the central nervous system. The disease primarily affects the white matter (myelin) of the brain, brain stem, and spinal cord, with a characteristic pattern visible on MRI. Elevated lactate levels can be detected in affected brain regions using magnetic resonance spectroscopy. The hallmark clinical features of LBSL include slowly progressive cerebellar ataxia (difficulty with coordination and balance), spasticity (muscle stiffness, particularly in the legs), and dorsal column dysfunction leading to impaired proprioception (sense of body position) and vibration sense. Patients typically present in childhood or adolescence with difficulty walking, though onset can range from infancy to adulthood. Additional symptoms may include dysarthria (slurred speech), cognitive decline (though often mild), and in some cases epilepsy. The severity and rate of progression are highly variable; some individuals become wheelchair-dependent in adolescence, while others maintain ambulation into adulthood. There is currently no cure or disease-modifying treatment for LBSL. Management is supportive and symptomatic, including physical therapy to maintain mobility, occupational therapy, speech therapy for dysarthria, and antispasticity medications. Orthopedic interventions may be needed for skeletal complications. Regular neurological monitoring and MRI follow-up are recommended. Genetic counseling is important for affected families.

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