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Genetics Home Reference: your guide to understanding genetic conditions
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Leukoencephalopathy with brainstem and spinal cord involvement and lactate elevation

(often shortened to LBSL)
Reviewed August 2011

What is LBSL?

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).

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.

Related Gene(s)

Changes in this gene are associated with leukoencephalopathy with brainstem and spinal cord involvement and lactate elevation.

  • DARS2

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 or management of LBSL?

These resources address the diagnosis or management of LBSL and may include treatment providers.

  • Gene Review: Leukoencephalopathy with Brain Stem and Spinal Cord Involvement and Lactate Elevation (http://www.ncbi.nlm.nih.gov/books/NBK43417)
  • Genetic Testing Registry: Leukoencephalopathy with Brainstem and Spinal Cord Involvement and Lactate Elevation (http://www.ncbi.nlm.nih.gov/gtr/conditions/C1970180)

You might also find information on the diagnosis or management of LBSL in Educational resources (http://www.ghr.nlm.nih.gov/condition/leukoencephalopathy-with-brainstem-and-spinal-cord-involvement-and-lactate-elevation/show/Educational+resources) and Patient support (http://www.ghr.nlm.nih.gov/condition/leukoencephalopathy-with-brainstem-and-spinal-cord-involvement-and-lactate-elevation/show/Patient+support).

General information about the diagnosis (http://ghr.nlm.nih.gov/handbook/consult/diagnosis) and management (http://ghr.nlm.nih.gov/handbook/consult/treatment) of genetic conditions is available in the Handbook. Read more about genetic testing (http://ghr.nlm.nih.gov/handbook/testing), particularly the difference between clinical tests and research tests (http://ghr.nlm.nih.gov/handbook/testing/researchtesting).

To locate a healthcare provider, see How can I find a genetics professional in my area? (http://ghr.nlm.nih.gov/handbook/consult/findingprofessional) 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.

You may also be interested in these resources, which are designed for healthcare professionals and researchers.

What other names do people use for LBSL?

  • mitochondrial aspartyl-tRNA synthetase deficiency

For more information about naming genetic conditions, see the Genetics Home Reference Condition Naming Guidelines (http://ghr.nlm.nih.gov/ConditionNameGuide) and How are genetic conditions and genes named? (http://ghr.nlm.nih.gov/handbook/mutationsanddisorders/naming) in the Handbook.

What if I still have specific questions about LBSL?

Ask the Genetic and Rare Diseases Information Center (http://rarediseases.info.nih.gov/GARD/).

What glossary definitions help with understanding LBSL?

acids ; amino acid ; aspartic acid ; ataxia ; autosomal ; autosomal recessive ; axons ; brainstem ; cell ; compound ; cytoplasm ; deficiency ; dysarthria ; enzyme ; epilepsy ; fever ; gene ; heterozygous ; homozygous ; imaging ; inherited ; lactate ; leukoencephalopathy ; magnetic resonance imaging ; mitochondria ; mutation ; nerve cell ; neurological ; nucleus ; prevalence ; protein ; pyramidal tract ; recessive ; spasticity ; synthesis ; tissue ; trauma ; tRNA ; white matter

You may find definitions for these and many other terms in the Genetics Home Reference Glossary (http://www.ghr.nlm.nih.gov/glossary).

References

  • Gene Review: Leukoencephalopathy with Brain Stem and Spinal Cord Involvement and Lactate Elevation (http://www.ncbi.nlm.nih.gov/books/NBK43417)
  • Lin J, Chiconelli Faria E, Da Rocha AJ, Rodrigues Masruha M, Pereira Vilanova LC, Scheper GC, Van der Knaap MS. Leukoencephalopathy with brainstem and spinal cord involvement and normal lactate: a new mutation in the DARS2 gene. J Child Neurol. 2010 Nov;25(11):1425-8. doi: 10.1177/0883073810370897. Epub 2010 May 25. (http://www.ncbi.nlm.nih.gov/pubmed/20501884?dopt=Abstract)
  • Scheper GC, van der Klok T, van Andel RJ, van Berkel CG, Sissler M, Smet J, Muravina TI, Serkov SV, Uziel G, Bugiani M, Schiffmann R, Krägeloh-Mann I, Smeitink JA, Florentz C, Van Coster R, Pronk JC, van der Knaap MS. Mitochondrial aspartyl-tRNA synthetase deficiency causes leukoencephalopathy with brain stem and spinal cord involvement and lactate elevation. Nat Genet. 2007 Apr;39(4):534-9. Epub 2007 Mar 25. (http://www.ncbi.nlm.nih.gov/pubmed/17384640?dopt=Abstract)
  • Uluc K, Baskan O, Yildirim KA, Ozsahin S, Koseoglu M, Isak B, Scheper GC, Gunal DI, van der Knaap MS. Leukoencephalopathy with brain stem and spinal cord involvement and high lactate: a genetically proven case with distinct MRI findings. J Neurol Sci. 2008 Oct 15;273(1-2):118-22. doi: 10.1016/j.jns.2008.06.002. Epub 2008 Jul 10. (http://www.ncbi.nlm.nih.gov/pubmed/18619624?dopt=Abstract)
  • van der Knaap MS, van der Voorn P, Barkhof F, Van Coster R, Krägeloh-Mann I, Feigenbaum A, Blaser S, Vles JS, Rieckmann P, Pouwels PJ. A new leukoencephalopathy with brainstem and spinal cord involvement and high lactate. Ann Neurol. 2003 Feb;53(2):252-8. (http://www.ncbi.nlm.nih.gov/pubmed/12557294?dopt=Abstract)

 

The resources on this site should not be used as a substitute for professional medical care or advice. Users seeking information about a personal genetic disease, syndrome, or condition should consult with a qualified healthcare professional. See How can I find a genetics professional in my area? (http://ghr.nlm.nih.gov/handbook/consult/findingprofessional) in the Handbook.

 
Reviewed: August 2011
Published: October 20, 2014