Leukoencephalopathy with Brain Stem and Spinal Cord Involvement and Lactate Elevation

Clinical characteristics Leukoencephalopathy with brain stem and spinal cord involvement and lactate elevation (LBSL) is characterized by slowly progressive cerebellar ataxia and spasticity with dorsal column dysfunction (decreased position and vibration sense) in most patients. The neurologic dysfunction involves the legs more than the arms. The tendon reflexes are retained. Deterioration of motor skills usually starts in childhood or adolescence, but occasionally not until adulthood. Dysarthria develops over time. Occasional findings include: epilepsy; learning problems; cognitive decline; and reduced consciousness, neurologic deterioration, and fever following minor head trauma. Many affected individuals become wheelchair dependent in their teens or twenties. Neonatal or early-infantile onset patients have a severe disease course and may die, whereas late-infantile and early-childhood onset is associated with early wheelchair dependency. Diagnosis/testing The diagnosis of LBSL can be made with confidence in persons with characteristic abnormalities observed on brain and spinal cord MRI and identification of biallelic pathogenic variants in DARS2, encoding mitochondrial aspartyl tRNA synthase. Management Treatment of manifestations: Supportive therapy includes physical therapy and rehabilitation to improve motor function, and the following as needed: antiepileptic drugs (AED), special education, speech therapy. Prevention of secondary complications: Rehabilitation and physical therapy are helpful in the prevention of secondary complications such as contractures and scoliosis. Genetic counseling LBSL is inherited in an autosomal recessive manner. At conception, each sib of an affected individual has a 25% chance of being affected, a 50% chance of being an asymptomatic carrier, and a 25% chance of being unaffected and not a carrier. Carrier testing for at-risk family members and prenatal testing for pregnancies at increased risk are possible if the pathogenic variants have been identified in the family.