What is LBSL?
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Leukoencephalopathy with brainstem and spinal cord involvement and
lactate elevation (commonly referred to as LBSL) is a progressive
disorder that affects the brain and spinal cord. Leukoencephalopathy
refers to abnormalities in the white matter of the brain, which is
tissue containing nerve cell fibers (axons) that transmit nerve
impulses.
Most affected individuals begin to develop movement problems during childhood or adolescence. However, in some individuals, these problems do not develop until adulthood. People with LBSL have abnormal muscle stiffness (spasticity) and difficulty with coordinating movements (ataxia). In addition, affected individuals lose the ability to sense the position of their limbs or vibrations with their limbs. These movement and sensation problems affect the legs more than the arms, making walking difficult. Most affected individuals eventually require wheelchair assistance, sometimes as early as their teens, although the age varies.
People with LBSL can have other signs and symptoms of the condition. Some affected individuals develop recurrent seizures (epilepsy), speech difficulties (dysarthria), learning problems, or mild deterioration of mental functioning. Some people with this disorder are particularly vulnerable to severe complications following minor head trauma, which may trigger a loss of consciousness, other reversible neurological problems, or fever.
Distinct changes in the brains of people with LBSL can be seen using magnetic resonance imaging (MRI). These characteristic abnormalities typically involve particular parts of the white matter of the brain and specific regions (called tracts) within the brain stem and spinal cord, especially the pyramidal tract and the dorsal column. In addition, most affected individuals have a high level of a substance called lactate in the white matter of the brain, which is identified using another test called magnetic resonance spectroscopy (MRS).
Most affected individuals begin to develop movement problems during childhood or adolescence. However, in some individuals, these problems do not develop until adulthood. People with LBSL have abnormal muscle stiffness (spasticity) and difficulty with coordinating movements (ataxia). In addition, affected individuals lose the ability to sense the position of their limbs or vibrations with their limbs. These movement and sensation problems affect the legs more than the arms, making walking difficult. Most affected individuals eventually require wheelchair assistance, sometimes as early as their teens, although the age varies.
People with LBSL can have other signs and symptoms of the condition. Some affected individuals develop recurrent seizures (epilepsy), speech difficulties (dysarthria), learning problems, or mild deterioration of mental functioning. Some people with this disorder are particularly vulnerable to severe complications following minor head trauma, which may trigger a loss of consciousness, other reversible neurological problems, or fever.
Distinct changes in the brains of people with LBSL can be seen using magnetic resonance imaging (MRI). These characteristic abnormalities typically involve particular parts of the white matter of the brain and specific regions (called tracts) within the brain stem and spinal cord, especially the pyramidal tract and the dorsal column. In addition, most affected individuals have a high level of a substance called lactate in the white matter of the brain, which is identified using another test called magnetic resonance spectroscopy (MRS).
How common is LBSL?
LBSL is a rare condition. Its exact prevalence is not known.
What genes are related to LBSL?
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.
Read more about the DARS2 gene.
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.
Read more about the DARS2 gene.
How do people inherit LBSL?
LBSL is inherited in an autosomal recessive pattern, which means both
copies of the gene in each cell have mutations. In this condition, each
copy of the gene carries a different mutation (compound heterozygous
mutations). An affected individual never has the same mutation in both
copies of the gene (a homozygous mutation). The parents of an individual
with an autosomal recessive condition each carry one copy of the
mutated gene, but they typically do not show signs and symptoms of the
condition.
Where can I find information about diagnosis, management, or treatment of LBSL?
These resources address the diagnosis or management of LBSL and may include treatment providers.
To locate a healthcare provider, see How can I find a genetics professional in my area? in the Handbook.
- Gene Review: Leukoencephalopathy with Brainstem and Spinal Cord Involvement and Lactate
Elevation - Gene Tests: Leukoencephalopathy with Brainstem and Spinal Cord Involvement and Lactate
Elevation
To locate a healthcare provider, see How can I find a genetics professional in my area? in the Handbook.
Where can I find additional information about LBSL?
You may find the following resources about LBSL helpful. These materials are written for the general public.-
MedlinePlus - Health information (4 links)
- Additional NIH Resources - National Institutes of Health
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Educational resources - Information pages (2 links)
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Patient support - For patients and families (3 links)
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