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Disease Profile

Leukoencephalopathy with brain stem and spinal cord involvement and lactate elevation

Prevalence
Prevalence estimates on Rare Medical Network websites are calculated based on data available from numerous sources, including US and European government statistics, the NIH, Orphanet, and published epidemiologic studies. Rare disease population data is recognized to be highly variable, and based on a wide variety of source data and methodologies, so the prevalence data on this site should be assumed to be estimated and cannot be considered to be absolutely correct.
<1 / 1 000 000

< 331

US Estimated

< 514

Europe Estimated

Age of onset

Childhood

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ICD-10

E88.8

Inheritance

Autosomal dominant A pathogenic variant in only one gene copy in each cell is sufficient to cause an autosomal dominant disease

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Autosomal recessive Pathogenic variants in both copies of each gene of the chromosome are needed to cause an autosomal recessive disease and observe the mutant phenotype

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X-linked
dominant X-linked dominant inheritance, sometimes referred to as X-linked dominance, is a mode of genetic inheritance by which a dominant gene is carried on the X chromosome.

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X-linked
recessive Pathogenic variants in both copies of a gene on the X chromosome cause an X-linked recessive disorder

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Mitochondrial or multigenic Mitochondrial genetic disorders can be caused by changes (mutations) in either the mitochondrial DNA or nuclear DNA that lead to dysfunction of the mitochondria and inadequate production of energy.

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Multigenic or multifactor Inheritance involving many factors, of which at least one is genetic but none is of overwhelming importance, as in the causation of a disease by multiple genetic and environmental factors.

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Not applicable

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Other names (AKA)

Leukoencephalopathy with brain stem and spinal cord involvement high lactate; LBSL; Leukoencephalopathy with brain stem and spinal cord involvement lactate elevation;

Categories

Congenital and Genetic Diseases; Metabolic disorders; Nervous System Diseases

Summary

Leukoencephalopathy with brain stem and spinal cord involvement and lactate elevation (LBSL) is a rare neurological disease characterized by slowly progressive cerebellar ataxia (lack of control of the movements) and spasticity with dorsal column dysfunction (decreased position and vibration sense) in most patients. The disease involves the legs more than the arms. It usually starts in childhood or adolescence, but in some cases not until adulthood. Difficulty speaking develops over time. Other symptoms may 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. The earlier the onset the more severe the disease is. The diagnosis is made in persons who had the characteristic abnormalities observed on brain and spinal cord MRI scans and with the genetic test identifiying the DARS2 gene alteration (mutation). There is still no cure and treatment is supportive and includes physical therapy and rehabilitation to improve movement function, and the following as needed: antiepileptic drugs, special education and speech therapy.[1]

Symptoms

This table lists symptoms that people with this disease may have. For most diseases, symptoms will vary from person to person. People with the same disease may not have all the symptoms listed. This information comes from a database called the Human Phenotype Ontology (HPO) . The HPO collects information on symptoms that have been described in medical resources. The HPO is updated regularly. Use the HPO ID to access more in-depth information about a symptom.

Medical Terms Other Names
Learn More:
HPO ID
80%-99% of people have these symptoms
Abnormality of the dorsal column of the spinal cord
0011397
30%-79% of people have these symptoms
Babinski sign
0003487
Clumsiness
0002312
Difficulty walking
Difficulty in walking
0002355
Distal muscle weakness
Weakness of outermost muscles
0002460
Dysarthria
Difficulty articulating speech
0001260
Dysmyelinating leukodystrophy
0006978
Progressive cerebellar ataxia
0002073
Progressive inability to walk
0002505
Progressive spasticity
0002191
Spastic ataxia
0002497
Tremor
0001337
Unsteady gait
Unsteady walk
0002317
5%-29% of people have these symptoms
Cognitive impairment
Abnormality of cognition
Cognitive abnormality
Cognitive defects
Cognitive deficits
Intellectual impairment
Mental impairment

[ more ]

0100543
Hyporeflexia
Decreased reflex response
Decreased reflexes

[ more ]

0001265
Impaired distal proprioception
0006858
Impaired vibration sensation in the lower limbs
Decreased lower limb vibratory sense
Decreased vibratory sense in lower limbs
Decreased vibratory sense in the lower extremities
Decreased vibratory sense in the lower limbs
Diminished vibratory sensation in the legs

[ more ]

0002166
Impaired visuospatial constructive cognition
0010794
Increased CSF lactate
0002490
Increased serum lactate
0002151
Leg muscle stiffness
0008969
Mental deterioration
Cognitive decline
Cognitive decline, progressive
Intellectual deterioration
Progressive cognitive decline

[ more ]

0001268
Motor delay
0001270
Peripheral axonal neuropathy
0003477
Poor fine motor coordination
0007010
1%-4% of people have these symptoms
Absent speech
Absent speech development
Lack of language development
Lack of speech
No speech development
No speech or language development
Nonverbal

[ more ]

0001344
Cerebellar atrophy
Degeneration of cerebellum
0001272
Cerebral atrophy
Degeneration of cerebrum
0002059
Diplopia
Double vision
0000651
Flexion contracture
Flexed joint that cannot be straightened
0001371
Generalized limb muscle atrophy
Generalized muscle wasting
0009055
Hearing impairment
Deafness
Hearing defect

[ more ]

0000365
Hypoplasia of the corpus callosum
Underdevelopment of part of brain called corpus callosum
0002079
Impaired pursuit initiation and maintenance
0007668
Intellectual disability
Mental deficiency
Mental retardation
Mental retardation, nonspecific
Mental-retardation

[ more ]

0001249
Muscular hypotonia
Low or weak muscle tone
0001252
Nystagmus
Involuntary, rapid, rhythmic eye movements
0000639
Optic atrophy
0000648
Polyneuropathy
Peripheral nerve disease
0001271
Ptosis
Drooping upper eyelid
0000508
Seizure
0001250
Slow saccadic eye movements
Slow eye movements
0000514
Slurred speech
0001350
Spastic/hyperactive bladder
0005340
Truncal ataxia
Instability or lack of coordination of central trunk muscles
0002078
Percent of people who have these symptoms is not available through HPO
Ataxia
0001251
Autosomal recessive inheritance
0000007
Hyperreflexia
Increased reflexes
0001347
Leukoencephalopathy
0002352
Muscle weakness
Muscular weakness
0001324
Skeletal muscle atrophy
Muscle degeneration
Muscle wasting

[ more ]

0003202
Slow progression
Signs and symptoms worsen slowly with time
0003677
Spasticity
Involuntary muscle stiffness, contraction, or spasm
0001257
Variable expressivity
0003828

Organizations

Support and advocacy groups can help you connect with other patients and families, and they can provide valuable services. Many develop patient-centered information and are the driving force behind research for better treatments and possible cures. They can direct you to research, resources, and services. Many organizations also have experts who serve as medical advisors or provide lists of doctors/clinics. Visit the group’s website or contact them to learn about the services they offer. Inclusion on this list is not an endorsement by GARD.

Organizations Providing General Support

    Learn more

    These resources provide more information about this condition or associated symptoms. The in-depth resources contain medical and scientific language that may be hard to understand. You may want to review these resources with a medical professional.

    Where to Start

    • Genetics Home Reference (GHR) contains information on Leukoencephalopathy with brain stem and spinal cord involvement and lactate elevation . This website is maintained by the National Library of Medicine.

      In-Depth Information

      • The Monarch Initiative brings together data about this condition from humans and other species to help physicians and biomedical researchers. Monarch’s tools are designed to make it easier to compare the signs and symptoms (phenotypes) of different diseases and discover common features. This initiative is a collaboration between several academic institutions across the world and is funded by the National Institutes of Health. Visit the website to explore the biology of this condition.
      • Online Mendelian Inheritance in Man (OMIM) is a catalog of human genes and genetic disorders. Each entry has a summary of related medical articles. It is meant for health care professionals and researchers. OMIM is maintained by Johns Hopkins University School of Medicine. 
      • Orphanet is a European reference portal for information on rare diseases and orphan drugs. Access to this database is free of charge.

        References

        1. van der Knaap MS & Salomons GS. Leukoencephalopathy with Brain Stem and Spinal Cord Involvement and Lactate Elevation. GeneReviews. February 12, 2015; https://www.ncbi.nlm.nih.gov/books/NBK43417/. Accessed 6/24/2015.