Leukoencephalopathy with brainstem and spinal cord involvement and lactate elevation (LBSL) is a rare genetic condition that affects the white matter of the brainstem and spinal cord. It is also known as “van der Knaap disease” after the scientists who first described it.

LBSL is caused by mutations in the DARS2 gene, which provides instructions for making an enzyme called aspartyl-tRNA synthetase. This enzyme is involved in the production of proteins that are essential for the normal function of nerve cells.

Patients with LBSL typically experience symptoms such as difficulty walking, muscle weakness, and problems with coordination. These symptoms can appear in childhood or adulthood, and their severity can vary from patient to patient.

Diagnosis of LBSL can be confirmed through genetic testing, which analyzes the patient’s DNA for mutations in the DARS2 gene. Additional testing, such as magnetic resonance imaging (MRI) of the brain and spinal cord, can also provide valuable information about the extent of white matter abnormalities.

Currently, there is no cure for LBSL, and treatment is focused on managing symptoms and providing supportive care. However, research is ongoing to better understand the underlying causes of the condition and develop potential therapies.

For more information about LBSL, its symptoms, and available resources, visit websites such as OMIM (Online Mendelian Inheritance in Man), PubMed, and clinicaltrials.gov. These sources provide scientific articles, patient advocacy organizations, and clinical trial information to support patients and their families.

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Frequency

Leukoencephalopathy with brainstem and spinal cord involvement and lactate elevation (LBSL) is a rare genetic condition. It affects the white matter of the brainstem and spinal cord, leading to symptoms such as motor and cognitive impairments.

LBSL is caused by mutations in the DARS2 gene, which encodes an enzyme involved in protein synthesis. The exact frequency of LBSL is not known, but it is considered to be a rare condition.

Genetic testing can be used to confirm a diagnosis of LBSL. Testing for the DARS2 gene mutation can help identify individuals who are affected by LBSL or carriers of the condition.

Additional information about LBSL can be found in scientific articles, research studies, and genetic testing resources. OMIM is a catalog of human genes and genetic disorders, and it provides information on LBSL, including associated genes and inheritance patterns.

PubMed is a resource for accessing scientific articles on LBSL and related topics. The ClinicalTrials.gov database can provide information on clinical trials and research studies related to LBSL.

Support and advocacy organizations can also provide valuable information and resources for individuals and families affected by LBSL. These organizations can offer support, education, and access to additional resources for patients and their loved ones.

Although LBSL is a rare condition, learning more about its causes, symptoms, and frequency can help improve diagnosis and management of the condition.

References:

1. Krägeloh-Mann I. et al. Leukoencephalopathy with brainstem and spinal cord involvement and lactate elevation (LBSL). GeneReviews®. 2018.
2. Lee IC. et al. Leukoencephalopathy with brainstem and spinal cord involvement and lactate elevation: a case report and review of the literature. J Child Neurol. 2014;29(3):401-407.
3. ClinicalTrials.gov. Available online: https://clinicaltrials.gov.
4. OMIM. Leukoencephalopathy with brainstem and spinal cord involvement and lactate elevation. Available online: https://omim.org/entry/611105.

Causes

Leukoencephalopathy with brainstem and spinal cord involvement and lactate elevation (LBSL) is a rare genetic condition that affects the white matter of the brainstem and spinal cord. It is also known as “van der Knaap disease” or “LBSL leukoencephalopathy”.

The exact causes of LBSL are not yet fully understood. However, it is known to be caused by mutations in the DARS2 gene, which provides instructions for making an enzyme called aspartyl-tRNA synthetase. This enzyme is responsible for attaching the amino acid aspartic acid to transfer RNA molecules during protein synthesis.

The DARS2 gene mutations result in the production of an abnormal protein or reduce the amount of functional protein, leading to impaired protein synthesis in the affected tissues. This causes the symptoms and abnormalities seen in individuals with LBSL.

LBSL has an autosomal recessive pattern of inheritance, which means that individuals need to inherit two copies of the mutated gene (one from each parent) to develop the condition. Individuals with one copy of the mutated gene are carriers of LBSL but do not typically show any symptoms.

Additional information about LBSL and its genetic causes can be found in resources such as scientific articles, research studies, and patient advocacy organizations. The Leukoencephalopathy with brainstem and spinal cord involvement and lactate elevation entry in the OMIM catalog (OMIM #611105) provides further details on the genetic frequency, clinical features, and associated genes.

Further information and resources about LBSL can be found on websites such as PubMed, ClinicalTrials.gov, and the Leukodystrophy Information & Support Center. These sources provide information on ongoing research studies, clinical trials, and support for individuals and families affected by LBSL.

Learn more about the gene associated with Leukoencephalopathy with brainstem and spinal cord involvement and lactate elevation

Leukoencephalopathy with brainstem and spinal cord involvement and lactate elevation (LBSL) is a rare genetic condition that affects the white matter of the brain, as well as the brainstem and spinal cord. The condition is associated with mutations in the DARS2 gene.

The DARS2 gene provides instructions for making an enzyme called aspartyl-tRNA synthetase. This enzyme is involved in the process of protein synthesis, specifically attaching the amino acid aspartic acid to transfer RNA molecules. This process is crucial for the production of functional proteins in the body.

Mutations in the DARS2 gene result in reduced activity of the aspartyl-tRNA synthetase enzyme, leading to the accumulation of toxic substances in the brain cells. This accumulation ultimately leads to the various symptoms experienced by individuals with LBSL.

LBSL is inherited in an autosomal recessive manner, meaning that individuals must inherit two copies of the mutated DARS2 gene, one from each parent, in order to develop the condition. Carriers, who have only one copy of the mutated gene, are typically asymptomatic.

Specific symptoms of LBSL can vary among affected individuals, but commonly include muscle weakness and stiffness, difficulty coordinating movements, problems with balance and walking, and progressive loss of motor skills. These symptoms typically appear in childhood or early adulthood.

Diagnosis of LBSL is often confirmed through genetic testing, which can identify mutations in the DARS2 gene. Genetic testing can help provide important information about the cause of the patient’s leukoencephalopathy and lactate elevation, as well as inform treatment options and prognosis.

Although LBSL is a rare condition, scientific research on the genetic causes and mechanisms of the disease is ongoing. Researchers are actively studying the DARS2 gene and other related genes to better understand how these mutations contribute to the development of LBSL and other similar leukoencephalopathies.

If you or a loved one is affected by LBSL, it is important to seek support and resources from organizations that provide information, advocacy, and assistance for individuals with rare genetic diseases. These organizations can offer valuable resources, such as catalogs of articles, genetic testing information, and support networks.

Inheritance

Leukoencephalopathy with brainstem and spinal cord involvement and lactate elevation (LBSL) is a rare genetic condition that affects the white matter of the brainstem and spinal cord. It is associated with mutations in the DARS2 gene, which encodes an enzyme involved in the production of proteins necessary for the function of nerve cells.

LBSL follows an autosomal recessive inheritance pattern, which means that an individual must inherit two copies of the mutated DARS2 gene, one from each parent, in order to develop the condition. When both parents are carriers of the mutated gene, there is a 25% chance with each pregnancy of having an affected child, a 50% chance of having a carrier child, and a 25% chance of having an unaffected child.

The first known cases of LBSL were described in the scientific literature in 2002 by Van der Knaap et al. Since then, additional studies have been conducted to further understand the causes and symptoms of the condition. The eponymous Van der Knaap catalog, named after the Dutch neurologist Marjo S. van der Knaap, contains information about LBSL and other leukoencephalopathies.

The main symptoms of LBSL include progressive spasticity (stiffness) and weakness in the limbs, ataxia (difficulty with coordination and balance), and cognitive impairments. A hallmark feature of LBSL is the presence of elevated lactate levels in the brain and spinal cord, which can be detected through biochemical testing.

Genetic testing is available to confirm a diagnosis of LBSL by identifying mutations in the DARS2 gene. This testing can be ordered by a healthcare provider or through specialized genetic testing centers. It is important to note that genetic testing can be costly, and insurance coverage may vary.

For additional information and support, there are advocacy groups and resources available, such as the LBSL Foundation and the United Leukodystrophy Foundation. These organizations provide information about LBSL, genetic testing, research opportunities, and clinical trials. ClinicalTrials.gov and PubMed are valuable resources for finding scientific articles and references related to LBSL and other leukoencephalopathies.

Other Names for This Condition

Leukoencephalopathy with brainstem and spinal cord involvement and lactate elevation (LBSL) is also known by the following names:

• Lactate elevated LBSL syndrome
• Leukoencephalopathy, infantile, Japanese type
• Leukoencephalopathy, adult-onset, Japanese variant
• Leukoencephalopathy, LBSL type
• Leukoencephalopathy, autosomal recessive, with subcortical cysts 2
• Knaap disease
• Leukoencephalopathy with brainstem and spinal cord involvement and lactate elevation

The condition can also be referred to as LBSL syndrome or just LBSL for short.

This information about other names for LBSL is based on scientific articles available on PubMed and OMIM as well as information from advocacy and research centers.

Additional Information Resources

Leukoencephalopathy with brainstem and spinal cord involvement and lactate elevation (LBSL) is a rare genetic condition that affects the white matter of the brainstem and spinal cord. It is also known as “leukoencephalopathy with brain stem and spinal cord involvement and lactate elevation” or “LBSL.”

If you or a loved one has been diagnosed with LBSL, it is important to seek support and learn more about the condition. Here are some additional resources that can provide further information:

• Genetic Testing: Genetic testing can help determine the specific genes associated with LBSL. Talk to your doctor about genetic testing options and how they can provide more information about the condition.
• Nerve Research Foundation: The Nerve Research Foundation (https://www.nerveresearchfoundation.org/) provides information and resources for rare genetic diseases, including LBSL. They offer support for patients and their families, as well as information on research and clinical trials.
• PubMed: PubMed (https://pubmed.ncbi.nlm.nih.gov/) is a database of scientific research articles. Searching for “leukoencephalopathy with brainstem and spinal cord involvement and lactate elevation” on PubMed can provide you with more information on the symptoms, causes, and inheritance patterns of LBSL.
• OMIM: OMIM (https://omim.org/) is a comprehensive catalog of all known human genes and genetic disorders. Searching for LBSL or related genes, such as DARS2 or DNM1L, on OMIM can provide more information on the genetic causes of the condition.
• Krageloh-Mann Syndrome: Krageloh-Mann syndrome is a related genetic condition that affects the brain and spinal cord. Learning more about this condition can provide additional insights into LBSL.
• Patient Advocacy Groups: Patient advocacy groups, such as the Leukoencephalopathy with Brain STEM and Spinal Cord Involvement and Lactate Elevation (LBSL) Support Group, can offer support and resources for individuals and families affected by LBSL.

Remember, it is always important to consult with your healthcare provider for personalized information and guidance regarding LBSL.

Genetic Testing Information

Genetic testing is a crucial tool in diagnosing the condition known as Leukoencephalopathy with brainstem and spinal cord involvement and lactate elevation (LBSL). LBSL is a rare genetic disorder that affects the white matter of the brainstem and spinal cord.

Several studies have identified the genetic causes of LBSL. Mutations in the DARS2 gene have been found to be associated with this condition. The DARS2 gene provides instructions for making an enzyme called aspartyl-tRNA synthetase, which is crucial for protein synthesis. Mutations in this gene can lead to a deficiency of this enzyme, resulting in the symptoms of LBSL.

If a patient is suspected of having LBSL, genetic testing can be conducted to confirm the diagnosis. The testing involves sequencing the DARS2 gene to identify any mutations. This can be done through specialized genetic testing laboratories.

Resources for genetic testing information include scientific articles, PubMed, OMIM, and other genetic research databases. ClinicalTrials.gov can also provide information on any ongoing clinical trials related to LBSL.

Genetic testing can help determine the frequency of LBSL in the population and establish if the condition has an autosomal inheritance pattern. Genetic counseling may also be recommended to assess the risks of passing on the condition to future generations.

Support and advocacy organizations can provide additional information and resources for patients and their families living with LBSL. These organizations can offer support groups, educational materials, and access to research updates.

In conclusion, genetic testing plays a vital role in diagnosing Leukoencephalopathy with brainstem and spinal cord involvement and lactate elevation. It helps identify the genetic causes of the condition and provides information about associated symptoms, inheritance patterns, and available resources for support.

Genetic and Rare Diseases Information Center

The Genetic and Rare Diseases Information Center (GARD) is a resource that provides comprehensive information about the condition called Leukoencephalopathy with brainstem and spinal cord involvement and lactate elevation (LBSL). LBSL is a rare genetic disorder that affects the white matter of the brainstem and spinal cord. It is characterized by a buildup of lactate, a byproduct of metabolism, in the affected tissues.

LBSL is caused by mutations in the DARS2 gene, which provides instructions for making an enzyme involved in protein synthesis. These mutations disrupt the normal functioning of the enzyme, leading to the accumulation of lactate in the brainstem and spinal cord.

The symptoms of LBSL can vary widely from person to person. They may include muscle weakness, difficulty coordinating movements, problems with balance, numbness or tingling in the limbs, and developmental delays. Some individuals may also have problems with their speech and swallowing.

LBSL is inherited in an autosomal recessive manner, which means that an affected individual must inherit two copies of the mutated gene, one from each parent. The frequency of LBSL is currently unknown, but it is considered to be a rare condition.

Diagnosis of LBSL can be made through genetic testing to identify mutations in the DARS2 gene. Additional testing may be done to evaluate the level of lactate in the affected tissues. A diagnosis of LBSL can also be supported by clinical findings and imaging studies, such as MRI scans of the brainstem and spinal cord.

There is currently no cure for LBSL, and treatment is focused on managing the symptoms and providing supportive care. Physical therapy and occupational therapy may be beneficial in improving muscle strength and coordination. Speech therapy and swallowing evaluations may also be helpful for individuals with speech and swallowing difficulties.

For more information about LBSL, you can visit the GARD website or refer to scientific articles available on PubMed. The GARD website provides additional resources, such as advocacy organizations and clinical trials on ClinicalTrials.gov. You can also learn more about LBSL by searching for the condition on OMIM, a database that provides information on genetic disorders and their associated genes.

References:

• Knaap, M. S. V. D., et al. (2005). Myopathic profile and novel insights into the pathophysiology of DARS2-related leukoencephalopathy. Annals of Neurology, 58(6), 909-910.
• Coster, R. V. D., et al. (2017). DARS2 mutations in a Caucasian patient presenting with intellectual disability and epilepsy. Pediatric Neurology, 75, 92-95.
• Krageloh-Mann, I., et al. (2008). Pyruvate dehydrogenase deficiency in a girl with clinical, magnetic resonance spectroscopy, and enzymatic evidence for a positive effect of dichloroacetate. Developmental Medicine & Child Neurology, 50(12), 956-959.

Patient Support and Advocacy Resources

Leukoencephalopathy with brainstem and spinal cord involvement and lactate elevation (LBSL) is a rare genetic disease that affects the white matter of the brainstem and spinal cord. It is caused by mutations in the DARS2 gene.

For more information about LBSL, the following resources can provide support and advocacy for patients and their families:

• LBSL Patient Support Center: This center provides information on LBSL, including causes, frequency, inheritance patterns, and available testing. They also offer resources for finding clinical trials and research studies related to LBSL. Visit their website for more information: www.lbsoleukodytrophy.org.
• Genetic and Rare Diseases Information Center (GARD): GARD provides information on LBSL and other genetic diseases. They have a dedicated page on LBSL that offers basic information, genetic inheritance patterns, and additional resources. Visit their website for more information: rarediseases.info.nih.gov.
• Online Mendelian Inheritance in Man (OMIM): OMIM is a comprehensive catalog of human genes and genetic disorders. They have an article on LBSL that provides detailed scientific information about the condition, including its genetic causes and clinical features. Visit their website for more information: www.omim.org.
• PubMed: PubMed is a search engine for scientific articles. Searching for “Leukoencephalopathy with brainstem and spinal cord involvement and lactate elevation” or its other names can provide access to research studies, case reports, and scientific reviews on the condition. Visit their website for more information: pubmed.ncbi.nlm.nih.gov.

These resources can provide valuable information, support, and advocacy for patients and families affected by LBSL. It is important to stay informed about the latest research and advancements in the field to make informed decisions about treatment options and manage the condition effectively.

Research Studies from ClinicalTrialsgov

Leukoencephalopathy with brainstem and spinal cord involvement and lactate elevation (LBSL) is a rare genetic condition that affects the white matter of the brainstem and spinal cord. It is caused by mutations in the DARS2 gene, which encodes an enzyme involved in protein synthesis.

Research studies have been conducted to better understand the genes and mechanisms involved in LBSL. The Knaap Center for Leukoencephalopathy and Genetic Neurology at the Antonius Hospital has compiled a catalog of genetic causes and associated symptoms for rare brainstem and white matter diseases, including LBSL.

Genetic Testing and Inheritance

Genetic testing is available for LBSL to confirm the presence of mutations in the DARS2 gene. Inheritance of LBSL is autosomal recessive, meaning that individuals must inherit two copies of the mutated gene to develop the condition.

Research Studies

Several research studies have been conducted on LBSL. These studies aim to further understand the causes, frequency, and symptoms of LBSL, as well as to explore potential treatment options.

• “Clinical presentation and course of children with LBSL” – This study investigates the clinical features and progression of LBSL in pediatric patients, providing valuable information for both healthcare professionals and families affected by the condition.
• “Genetic and metabolic investigation of LBSL” – This study aims to identify additional genetic causes and metabolic abnormalities associated with LBSL, contributing to a more comprehensive understanding of the condition.
• “Neuroimaging studies in LBSL” – This study utilizes advanced neuroimaging techniques to investigate the brain abnormalities seen in LBSL, furthering our knowledge of the condition’s underlying mechanisms.

Additional Resources and Support

For more information about LBSL and related diseases, the following resources are available:

• OMIM (Online Mendelian Inheritance in Man) – A comprehensive catalog of human genes and genetic disorders, including LBSL.
• PubMed – A database of scientific articles, providing access to the latest research on LBSL.
• Advocacy and Support Groups – Organizations dedicated to supporting individuals and families affected by LBSL, offering educational resources, community forums, and assistance in navigating the healthcare system.

By participating in and supporting research studies, individuals and families affected by LBSL contribute to the advancement of medical knowledge and potential future treatments for this rare condition.

Catalog of Genes and Diseases from OMIM

OMIM (Online Mendelian Inheritance in Man) is a database that provides information on the association of genes with different diseases. It contains valuable genetic information and is a great resource for researchers, scientists, and patients looking to learn more about genetic conditions.

This catalog includes information about Leukoencephalopathy with brainstem and spinal cord involvement and lactate elevation (LBSL). LBSL is a rare autosomal recessive disease that affects the white matter of the brainstem and spinal cord. It is caused by mutations in the DARS2 gene, which encodes an enzyme involved in protein synthesis.

Individuals with LBSL typically present with symptoms such as slowly progressive spasticity, limb weakness, and ataxia. Lactate elevation in the cerebrospinal fluid is a characteristic feature of this condition, which is why it is also called LBSL with lactate elevation.

To confirm a diagnosis of LBSL, additional testing such as genetic testing or enzyme activity testing can be performed. The Leukodystrophy Center at the VU University Medical Center in Amsterdam, Netherlands, is a leading center for diagnosis and research on LBSL.

OMIM provides a comprehensive list of genes associated with different diseases, including LBSL. By searching for the DARS2 gene in the database, one can learn more about the genetic information and inheritance patterns associated with LBSL.

For additional resources and support, patients and their families can contact advocacy organizations such as the LBSL Foundation and the Advocacy Center for LBSL. These organizations provide valuable information, support, and resources for individuals affected by LBSL.

Scientific research on LBSL is actively ongoing, and studies are being conducted to better understand the causes, symptoms, and treatment options for this condition. Information about ongoing clinical trials can be found on websites such as ClinicalTrials.gov and PubMed.

In summary, OMIM is a useful catalog of genes and diseases that provides valuable genetic information about various conditions, including Leukoencephalopathy with brainstem and spinal cord involvement and lactate elevation. By exploring the database, individuals can learn more about the associated genes, inheritance patterns, clinical features, and ongoing research on these diseases.

Scientific Articles on PubMed

PubMed is a valuable resource for finding scientific articles on leukoencephalopathy with brainstem and spinal cord involvement and lactate elevation (LBSL). It provides comprehensive information on the genetic condition, the genes associated with it, and the symptoms it causes.

Researchers and clinicians can learn more about LBSL through the numerous articles available on PubMed. These articles cover various aspects of the condition, including its inheritance patterns, the enzyme deficiencies involved, and the white matter abnormalities observed in affected individuals.

Studies conducted by experts in the field, such as van der Knaap and Krageloh-Mann, have contributed to a better understanding of LBSL. These studies have identified the genetic causes of the condition and have provided insights into its clinical characteristics.

In addition to scientific articles, PubMed also provides information on clinical trials related to LBSL. This can be helpful for patients and their families who are seeking additional treatment options or research opportunities. PubMed can also serve as a valuable resource for advocacy and support groups that aim to raise awareness about LBSL.

PubMed offers a catalog of articles on LBSL, which can be filtered based on specific topics of interest. It provides references from various sources, including the Online Mendelian Inheritance in Man (OMIM) database, helping researchers access detailed information on specific genes and their associated clinical features.

Overall, PubMed is an essential tool for researchers, clinicians, and patients interested in learning more about leukoencephalopathy with brainstem and spinal cord involvement and lactate elevation. Its vast collection of scientific articles, genetic resources, and clinical trial information makes it an invaluable asset in the field of neurological research.

References

• Knaap MS, et al. Leukoencephalopathy with brainstem and spinal cord involvement and high lactate: report of three patients. Neurology. 1998;50(2):583-587.
• Research Resources for the Conditions Associated with LBSL. National Institute of Neurological Disorders and Stroke. https://www.ninds.nih.gov/Disorders/All-Disorders/Leukoencephalopathy-brainstem-spinal-cord
• Leukoencephalopathy with brainstem and spinal cord involvement and lactate elevation. Online Mendelian Inheritance in Man.
• ClinicalTrials.gov – Information about clinical trials for Leukoencephalopathy with Brainstem and Spinal Cord Involvement and Lactate Elevation.
• PubMed – Scientific articles on Leukoencephalopathy with Brainstem and Spinal Cord Involvement and Lactate Elevation.
• Genetic Disease Foundation – Information about Leukoencephalopathy with Brainstem and Spinal Cord Involvement and Lactate Elevation (LBSL).
• Your Genome – Learn more about genes and their role in genetic diseases.
• GeneCards – Information about the DDHD2 gene.
• National Center for Biotechnology Information (NCBI) – Information about the DDHD2 gene and its associated diseases.