What is LBSL (Leukoencephalopathy with Brain Stem and Spinal Cord Involvement and Lactate Elevation)?
LBSL is a rare genetic disorder that affects the brain and spinal cord. There are thought to be as many as 500 patients identified worldwide, but many people go undiagnosed or misdiagnosed.
LBSL is caused by mutations in the DARS2 gene. DARS2 provides the body with instructions for making an enzyme called mitochondrial aspartyl-tRNA synthetase. This enzyme helps with production of proteins in the mitochondria — the energy factories of our cells, which turn nutrients into energy — and is essential for myelin, the white matter that insulates nerves.
As a result of DARS2 mutations, certain parts of the nervous system do not have sufficient energy to function properly. This affects their function and the production of nerve coatings, called myelin. Much like the plastic coating around the wires in your home, myelin provides insulation to the nervous system and is essential for the transmission of signals from the brain to the rest of the body.
What Are the Symptoms of LBSL?
Symptoms of LBSL may include ataxia and balance impairment as well as loss of the ability to sense the position of their limbs, which for many results in the loss of independent walking. Many patients eventually require mobility aids and wheelchairs. LBSL also causes muscle stiffness or weakness and difficulty with coordination, as well as fine motor challenges and hot/cold intolerance.
While less common, seizures, speech difficulties, learning disabilities, or cognitive dysfunction can occur, and some patients are particularly vulnerable to severe complications, such as regressions, after fevers or head trauma.
How Do You Get LBSL?
LBSL is an autosomal recessive disorder, meaning patients inherited two DARS2 mutations, one from each parent.
How Is LBSL Diagnosed?
Symptom onset usually leads to an MRI, which shows characteristic white matter abnormalities. Genetic testing typically confirms the diagnosis.
Is There a Treatment?
There is no known cure, though researchers are working on gene therapy, ASO therapy and drug repurposing. Treatment addresses the symptoms and may include physical, occupational and speech therapy, medications and special education.