Question: What are the genetic changes related to leukoencephalopathy with brainstem and spinal cord involvement and lactate elevation ?
Answer: LBSL is caused by mutations in the DARS2 gene, which provides instructions for making an enzyme called mitochondrial aspartyl-tRNA synthetase. This enzyme is important in the production (synthesis) of proteins in cellular structures called mitochondria, the energy-producing centers in cells. While most protein synthesis occurs in the fluid surrounding the nucleus (cytoplasm), some proteins are synthesized in the mitochondria. During protein synthesis, in either the mitochondria or the cytoplasm, building blocks (amino acids) are connected together in a specific order, creating a chain of amino acids that forms the protein. Mitochondrial aspartyl-tRNA synthetase plays a role in adding the amino acid aspartic acid at the proper place in mitochondrial proteins. Mutations in the DARS2 gene result in decreased mitochondrial aspartyl-tRNA synthetase enzyme activity, which hinders the addition of aspartic acid to mitochondrial proteins. It is unclear how the gene mutations lead to the signs and symptoms of LBSL. Researchers do not understand why reduced activity of mitochondrial aspartyl-tRNA synthetase specifically affects certain parts of the brain and spinal cord.
Source: GHR