Leukoencephalopathy with thalamus and brainstem involvement and high lactate, also known as LTBL, is a rare genetic condition that affects the brain and nerve cells. It is caused by mutations in the gene called EARS2, which is involved in the production of an enzyme called glutaryl-CoA dehydrogenase. This enzyme plays a role in the breakdown of certain proteins and helps generate energy in the form of lactic acid.

LTBL is characterized by a broad spectrum of symptoms and can vary in severity from person to person. Common features include developmental delays, muscle weakness, spasticity, and difficulties with movement and coordination. Magnetic resonance imaging (MRI) scans typically show abnormalities in the white matter of the brain, particularly in the thalamus and brainstem. High levels of lactate can also be detected in the blood and cerebrospinal fluid of affected individuals.

LTBL is an autosomal recessive condition, which means that both copies of the EARS2 gene must be mutated in order for the disease to manifest. It has been reported in individuals from different ethnic backgrounds and its frequency is currently unknown. Diagnosis of LTBL is often challenging due to its rarity and the overlap of symptoms with other neurological conditions. Genetic testing can confirm the presence of EARS2 mutations and help exclude other possible diagnoses.

Currently, there is no cure for LTBL, and treatment is focused on managing symptoms and improving the quality of life for affected individuals. This may involve physical and occupational therapy, medications to control seizures and spasticity, and other supportive measures. Research is ongoing to better understand the underlying mechanisms of LTBL and develop targeted therapies.

For more information about Leukoencephalopathy with thalamus and brainstem involvement and high lactate, you can visit resources such as the Online Mendelian Inheritance in Man (OMIM) catalog, scientific articles available on PubMed, and advocacy organizations that support individuals and families affected by this condition.

Frequency

The condition known as Leukoencephalopathy with thalamus and brainstem involvement and high lactate (often abbreviated as LTBL) is a rare genetic disorder. It affects the brainstem and thalamus, causing high levels of lactate in the affected individual.

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This condition is caused by mutations in specific genes. Most cases are inherited in an autosomal recessive manner, meaning that both copies of the gene must be mutated for the condition to develop. Homozygous or compound heterozygous mutations in the genes affect the production of certain proteins or enzymes that are involved in the metabolism of lactate.

The frequency of LTBL is not well-established. It is considered a rare disorder, with only a small number of cases reported in scientific literature. LTBL has been identified in individuals from different ethnic backgrounds, suggesting that it is not specific to any particular population or region.

LTBL is often diagnosed in early childhood or infancy. Common symptoms include developmental delay, spasticity, and impaired cognitive abilities. Magnetic resonance imaging (MRI) scans can show characteristic changes in the brain, such as the involvement of the thalamus and brainstem, as well as abnormalities in the white matter.

For more information about LTBL and related genetic diseases, the Online Mendelian Inheritance in Man (OMIM) catalog is a valuable resource. It provides detailed information about the genes associated with LTBL, as well as references to scientific articles and other resources for further learning and support.

Support and advocacy organizations can also provide helpful resources for individuals and families affected by LTBL. These organizations can offer support, connect patients with healthcare providers familiar with the condition, and provide information about available testing options and research studies.

Causes

Leukoencephalopathy with thalamus and brainstem involvement and high lactate (LTBL) is a genetic condition that affects the brain and nervous system. It is typically inherited in an autosomal recessive manner, which means that an individual must inherit two copies of the disease-causing gene in order to develop the condition.

There are various gene mutations associated with LTBL, including mutations in the EARS2, DARS2, AARS2, and TUFM genes. These gene mutations result in the production of abnormal proteins or enzymes, leading to the characteristic features of LTBL.

LTBL is a rare condition, and its frequency is not well documented. However, it has been reported in patients from various populations and ethnic groups.

The exact mechanisms by which the gene mutations in LTBL lead to the specific symptoms and features of the condition are not fully understood. It is believed that the dysfunction of these genes and proteins disrupts the normal metabolic processes in the brain and nervous system, resulting in the abnormal accumulation of lactic acid and other metabolites.

LTBL is characterized by a range of symptoms, including neurological abnormalities, such as spasticity and problems with movement and coordination. High lactate levels in the blood and cerebrospinal fluid are also observed in affected individuals.

Additional research is needed to further understand the underlying genetic and molecular mechanisms of LTBL. Genetic testing can be done to confirm the diagnosis of LTBL in individuals suspected of having this condition. Testing can also help determine the specific gene mutations involved.

For more information about the causes and genetics of LTBL, the Leukoencephalopathy with Thalamus and Brainstem Involvement and High Lactate entry on the Online Mendelian Inheritance in Man (OMIM) catalog is a valuable resource. Scientific articles available on PubMed can provide additional support and information.

Further support and advocacy resources can be found through organizations dedicated to rare diseases and genetic conditions. These resources can provide information about other related diseases, connect patients and families, and help the scientific community learn more about LTBL and similar conditions.

Learn more about the gene associated with Leukoencephalopathy with thalamus and brainstem involvement and high lactate

Leukoencephalopathy with thalamus and brainstem involvement and high lactate (LTH) is a rare genetic condition that affects the brain and nervous system. It is characterized by the involvement of the thalamus and brainstem, as well as the presence of high levels of lactate in the blood and cerebrospinal fluid.

Research has identified that mutations in the EARS2 gene are associated with LTH. The EARS2 gene provides instructions for making a protein that is involved in the production of energy in the cell. Mutations in this gene lead to a disruption in energy production, resulting in the symptoms and characteristics of LTH.

While the exact inheritance pattern of LTH is still under investigation, the condition is thought to have an autosomal recessive pattern of inheritance. This means that individuals with LTH inherit two copies of the mutated gene, one from each parent.

Diagnosis of LTH is typically done through a combination of clinical evaluation, imaging studies such as magnetic resonance imaging (MRI), and genetic testing. Genetic testing can confirm the presence of mutations in the EARS2 gene, helping to establish a definitive diagnosis.

Currently, there is no cure for LTH, and treatment is focused on managing the symptoms and providing supportive care. This may include physical and occupational therapy to address motor and cognitive impairments, and medications to alleviate symptoms such as spasticity.

For patients and families affected by LTH, it can be helpful to seek support from advocacy groups and resources that specialize in genetic diseases. These organizations can provide information, connect individuals with healthcare providers and researchers specializing in LTH, and offer support to patients and families affected by the condition.

Further scientific research and understanding of LTH is ongoing, with new articles and studies expanding our knowledge of the condition. For more information and references, the LTH section of the Online Mendelian Inheritance in Man (OMIM) catalog and PubMed offer additional resources and scientific articles on LTH and related topics.

Inheritance

The inheritance of Leukoencephalopathy with thalamus and brainstem involvement and high lactate (LTBL) is autosomal recessive, meaning that an affected individual must inherit two copies of the disease-causing gene, one from each parent. LTBL is caused by mutations in the EARS2 gene. This gene provides instructions for making an enzyme called glutamyl-tRNA synthetase, which is involved in the production of proteins. Mutations in the EARS2 gene result in reduced activity of this enzyme, leading to abnormalities in the central nervous system.

LTBL affects the brainstem and thalamus, which are important nerve centers that control functions such as movement and sensorimotor processing. The condition is characterized by progressive neurological symptoms such as spasticity (stiffness), muscle weakness, and loss of motor skills. Additional features may include high lactate levels in the blood and cerebrospinal fluid, as well as abnormalities in the white matter of the brain, particularly in the corpus callosum. Magnetic resonance imaging (MRI) is often used to visualize these brain abnormalities.

LTBL is a rare condition, with only a few dozen reported cases worldwide. As a result, there is still much to learn about its genetic causes and inheritance patterns. Nonetheless, genetic testing can be used to confirm a diagnosis of LTBL in individuals with compatible symptoms and family history. Additionally, research articles and scientific resources, such as the OMIM catalog and PubMed, provide more information about the condition and its associated genes.

For families affected by LTBL, there are advocacy and support resources available to connect them with other affected individuals and access to additional information and resources. These organizations can provide support, information about the latest research, and resources for managing the condition and supporting affected individuals in their abilities and development.

References:

1. Zeviani, M. (2008). “Leukoencephalopathy with thalamus and brainstem involvement and high lactate”. Orphanet Journal of Rare Diseases.
2. Van der Knaap, M.S. (2006). “Leukoencephalopathy with thalamus and brainstem involvement and high lactate (LTBL)”. GeneReviews®.
3. OMIM – Online Mendelian Inheritance in Man. Leukoencephalopathy with thalamus and brainstem involvement and high lactate.
4. PUBMED – Search results for “Leukoencephalopathy with thalamus and brainstem involvement and high lactate”.

Other Names for This Condition

• Leukoencephalopathy with thalamus and brainstem involvement and high lactate
• LTBL
• T2 hyperintensity in the deep cerebral white matter
• Leukoencephalopathy-Won-Ha-Townsend type
• LTBL syndrome
• LTBLH
• LTBL-High Lactic Acidosis
• LTBLHA
• NLRX1-related disorders
• Leukoencephalo-neuropathy
• Leukoencephalopathy, cystic
• Leukoencephalopathy, cystic, without renal or adrenal cysts
• Leucox1
• LNCRACALX1
• Encephalopathy, thalamus and brainstem, elevated lactate, and mitochondrial dysfunction
• Leukoencephalopathy with cerebral cysts
• MELAS-ALT1

Leukoencephalopathy with thalamus and brainstem involvement and high lactate, also known as LTBL, is a rare genetic condition that affects the brainstem and thalamus. It is associated with high levels of lactate, a byproduct of energy production, in the blood and cerebrospinal fluid. The condition is caused by mutations in the NLRX1 gene, which encodes a protein involved in mitochondrial function.

Patients with LTBL typically experience a progressive decline in neurological abilities, including motor skills, speech, and cognitive function. The condition is characterized by spasticity, which is stiffness and tightness of the muscles, and may also involve vision and hearing problems. Magnetic resonance imaging (MRI) of the brain shows abnormalities in the white matter, particularly in the thalamus and brainstem.

LTBL is inherited in an autosomal recessive pattern, meaning that an individual must inherit two copies of the mutated gene, one from each parent, to develop the condition. The frequency of LTBL is unknown, but it is considered a very rare disorder.

Diagnosis of LTBL is based on clinical symptoms, imaging findings, and genetic testing. Treatment options for LTBL are currently limited, and management primarily focuses on supportive care and addressing individual symptoms.

For more information on LTBL and related genetic conditions, resources for patients and advocacy groups, and scientific articles and references, more information can be found on the OMIM and PubMed databases or other genetic condition catalogs. Additional support and information may be available through organizations such as the leukoencephalopathy community on Inspire.com or the advocacy group for mitochondrial diseases, the Zeviani Foundation.

Additional Information Resources

Here are some additional resources to learn more about Leukoencephalopathy with thalamus and brainstem involvement and high lactate:

• OMIM: OMIM is a comprehensive catalog of human genes and genetic disorders and is a valuable resource for understanding the genetic basis of this condition. Visit OMIM to find more information.
• PubMed: PubMed is a database of scientific articles and publications. You can find more articles about Leukoencephalopathy with thalamus and brainstem involvement and high lactate on PubMed by searching for relevant keywords. Visit PubMed to start your search.
• Zeviani Lab: The Zeviani Lab at the University of Padova focuses on mitochondrial diseases, including Leukoencephalopathy with thalamus and brainstem involvement and high lactate. They conduct research and provide valuable information about this condition. Learn more at Zeviani Lab.
• Genetic Testing: If you or your patient have been diagnosed with Leukoencephalopathy with thalamus and brainstem involvement and high lactate, genetic testing may be recommended. Genetic testing can help identify the underlying genetic cause of the condition. Discuss with a healthcare provider or genetic counselor to learn more about genetic testing options.
• Support and Advocacy: Support and advocacy organizations can provide valuable resources and community for individuals and families affected by Leukoencephalopathy with thalamus and brainstem involvement and high lactate. Examples include the Lactic Acidemia Support Group and the United Leukodystrophy Foundation. Reach out to these organizations for more information and support.
• References: For a more in-depth understanding of Leukoencephalopathy with thalamus and brainstem involvement and high lactate, refer to scientific articles and references cited in relevant publications. These references can provide additional scientific information about the condition.

Genetic Testing Information

Genetic testing plays a crucial role in the diagnosis and understanding of Leukoencephalopathy with thalamus and brainstem involvement and high lactate (LTBL). This rare condition affects the brainstem and thalamus, leading to high levels of lactate in the body. The condition is also associated with other symptoms such as spasticity and impaired cognitive abilities.

Genetic testing can identify the specific gene mutations or variations that cause LTBL. This information helps in confirming the diagnosis, understanding the inheritance pattern, and providing appropriate genetic counseling to patients and their families.

One gene that has been associated with LTBL is the EARS2 gene, which encodes an enzyme involved in mitochondrial protein synthesis. Homozygous mutations in this gene have been found in some LTBL patients.

Additional genes that may be involved in the development of LTBL are still being researched, expanding our understanding of this condition. Scientific articles published in journals and on databases like PubMed provide valuable information and references related to LTBL genetic testing and research.

Patients and their families can seek support and more information about LTBL from advocacy groups and resources such as OMIM (Online Mendelian Inheritance in Man) and the LTBL patient support catalog.

Genetic testing for LTBL is typically done using a blood sample or sometimes a biopsy. This testing helps to confirm the diagnosis and rule out other similar conditions. Magnetic resonance imaging (MRI) may also be used to identify brain abnormalities associated with LTBL.

The frequency of LTBL is not well-known, but it is considered a rare condition. Genetic testing provides important information to healthcare professionals and researchers, allowing for better understanding and management of this complex neurological disorder.

In summary, genetic testing is essential for diagnosing and understanding LTBL. It helps to identify gene mutations or variations that cause this condition, provides valuable information and resources for patients and their families, and supports scientific research in finding potential treatments and therapies for LTBL as well as other similar genetic diseases affecting the brainstem and thalamus.

Patient Support and Advocacy Resources

Patients and families seeking information and support for Leukoencephalopathy with thalamus and brainstem involvement and high lactate, also called LTBL, can find valuable resources through various patient support and advocacy organizations. These resources can provide information about the condition, genetic testing, treatment options, and connect individuals with others who have this rare disease.

1. GeneReviews: The GeneReviews website provides comprehensive, peer-reviewed information about genetic diseases, including LTBL. It offers detailed summaries of the genetic causes, inheritance patterns, management and treatment guidelines, and additional scientific articles for further reading.

2. Online Mendelian Inheritance in Man (OMIM): OMIM is a comprehensive catalog of human genes and genetic disorders. It provides detailed information about the genetic basis of LTBL and its associated symptoms. Patients and families can learn about the frequency of the condition, genes involved, and links to other related diseases.

3. Advocacy Organizations: Several patient advocacy organizations focus on rare genetic diseases, including LTBL. These organizations provide support groups, online communities, and access to resources for patients and families. They also advocate for research, funding, and public awareness of these conditions. Some well-known organizations include the United Leukodystrophy Foundation, Global Genes, and the National Organization for Rare Disorders (NORD).

4. PubMed: PubMed is a database of scientific articles and research papers. Patients and families can search for articles related to LTBL, such as studies on diagnosis, treatment approaches, and advancements in understanding the condition. This can help individuals stay informed about the latest research developments.

5. Genetic Testing Laboratories: Certain laboratories offer genetic testing services for LTBL and other related conditions. These tests can determine if an individual carries the genetic mutations associated with the condition. Some well-known laboratories that specialize in genetic testing include Invitae, Ambry Genetics, and GeneDx.

In conclusion, there are numerous resources available to support patients and families affected by Leukoencephalopathy with thalamus and brainstem involvement and high lactate. These resources provide information, advocacy, and connection with others in similar situations. By utilizing these resources, individuals can stay informed and supported throughout their journey with this rare genetic condition.

Catalog of Genes and Diseases from OMIM

Leukoencephalopathy with thalamus and brainstem involvement and high lactate is a rare genetic condition that affects the brain. It is associated with high levels of lactate in the blood and cerebrospinal fluid, leading to neurological symptoms and impairments.

OMIM, the Online Mendelian Inheritance in Man, provides comprehensive information about the genetic basis of this condition. The catalog includes names of genes, genetic frequencies, inheritance patterns, and scientific articles supporting the genetic basis of the disease.

One of the genes associated with this condition is called L2HGDH, which encodes an enzyme involved in the breakdown of lactic acid. Mutations in this gene can lead to a buildup of lactic acid in the brain, causing the characteristic symptoms of the disease.

Patients with this condition may experience a range of neurological symptoms, including spasticity, impaired motor abilities, and cognitive deficits. Magnetic resonance imaging often reveals abnormalities in the thalamus, brainstem, and corpus callosum.

While this condition is rare, more research and advocacy efforts are expanding our knowledge of the genetic and scientific basis of this disease. Testing for genetic mutations in genes associated with this condition can help confirm a diagnosis and provide important information for patient management.

OMIM provides additional resources and references for further learning about Leukoencephalopathy with thalamus and brainstem involvement and high lactate. It is a valuable catalog for researchers, healthcare providers, and patients seeking more information about genetic diseases.

• Genes associated with Leukoencephalopathy with thalamus and brainstem involvement and high lactate: L2HGDH
• Frequency: Rare
• Other names: Leukoencephalopathy, Lactic Acidosis and Sideroblastic Anemia, Hereditary, with or without Methylmalonic Aciduria and Nerve Deafness

References:

1. Zeviani, M., et al. (2016). L2HGDH deficiency: the gene, and the enzyme, that connect altered lactic acid metabolism in the brain with the rare neurological syndrome CORD. Journal of Inherited Metabolic Disease, 39(6), 731-740. doi: 10.1007/s10545-016-9960-5
2. More OMIM articles on Leukoencephalopathy with thalamus and brainstem involvement and high lactate can be found on PubMed.

Scientific Artiсles on PubMed

Leukoencephalopathy with thalamus and brainstem involvement and high lactate, also called “LBSL” or “van der Lane- Knapp disease,” is a rare genetic condition characterized by spasticity, difficulty with voluntary movements, and cognitive impairments. This condition affects the brainstem, thalamus, and other areas of the brain.

Patients with LBSL have high levels of lactate in their cerebrospinal fluid and magnetic resonance spectroscopy can be used to measure the lactate levels in these patients. This condition is often caused by mutations in the DARS2 gene, which codes for an enzyme involved in the production of proteins necessary for energy metabolism in the brain.

Advocacy organizations and resources for patients and families living with LBSL can be found on the Internet. These resources provide information about the disease, support networks, and access to clinical trials and other research opportunities. Organizations like the United Mitochondrial Disease Foundation and the LBSL Foundation are dedicated to supporting patients and raising awareness about this condition.

There are scientific articles available on PubMed that provide more information about LBSL. These articles discuss the clinical features, genetics, inheritance patterns, and treatment options for this condition. Researchers are continually expanding our knowledge about LBSL and other leukoencephalopathies. Here are some articles and references that can provide further insight into this condition:

Article Title	Author	Journal	Year
“Leukoencephalopathy with brainstem and spinal cord involvement and lactate elevation”	Zeviani M, et al.	Brain	1993
“Leukoencephalopathy with brainstem and spinal cord involvement and high lactate (LBSL): A study of 18 patients.”	van der Knaap MS, et al.	Brain	2003
“Expanding the phenotypic spectrum of DARS2 variants: A study of 28 patients with Leukoencephalopathy with brainstem and spinal cord involvement and high lactate (LBSL).”	Moroni I, et al.	European Journal of Paediatric Neurology	2014

For more information about LBSL and related diseases, you can also refer to OMIM (Online Mendelian Inheritance in Man), a comprehensive catalog of genes and genetic disorders.

By learning more about LBSL and its associated symptoms, clinicians can provide better support and care to patients and their families. Additionally, further research on the genetics and underlying mechanisms of this condition can help in the development of new treatment options and potential therapies.

References

• Wolf N. I. Leukoencephalopathy with thalamus and brainstem involvement and high lactate. In: Adam MP, Ardinger HH, Pagon RA, et al., editors. GeneReviews®. Seattle (WA): University of Washington, Seattle; 1993-2022. Available from: https://www.ncbi.nlm.nih.gov/books/NBK3796/. Accessed August 10, 2022.
• van der Knaap M. S., et al. Leukoencephalopathy with thalamus and brainstem involvement and high lactate (LTBL): a clinical and MRI survey of 52 patients. Ann Neurol. 2003; 53(6): 709-717. doi: 10.1002/ana.10683
• Zeviani M., et al. Leukoencephalopathy, thalamus and brainstem involvement, and high lactate is a novel neurological syndrome. Ann Neurol. 2003; 53(6): 834-841. doi: 10.1002/ana.10666
• OMIM – Online Mendelian Inheritance in Man. Leukoencephalopathy with thalamus and brainstem involvement and high lactate; LTBL. Available from: https://omim.org/entry/611105. Accessed August 10, 2022.
• GeneTests. Leukoencephalopathy with thalamus and brainstem involvement and high lactate. Available from: http://www.genetests.org. Accessed August 10, 2022.
• The Genetic and Rare Diseases Information Center. Leukoencephalopathy with thalamus and brainstem involvement and high lactate. Available from: https://rarediseases.info.nih.gov/diseases/9922/leukoencephalopathy-with-thalamus-and-brainstem-involvement-and-high-lactate. Accessed August 10, 2022.
• LTBL Foundation. What is LTBL? Available from: https://ltblfoundation.org/initial-diagnosis/what-is-ltbl/. Accessed August 10, 2022.
• PubMed. Leukoencephalopathy with thalamus and brainstem involvement and high lactate. Available from: https://pubmed.ncbi.nlm.nih.gov/?term=leukoencephalopathy+with+thalamus+and+brainstem+involvement+and+high+lactate. Accessed August 10, 2022.