Leukoencephalopathy with thalamus and brainstem involvement and high lactate

Disease Overview

Leukoencephalopathy with thalamus and brainstem involvement and high lactate (LTBL) is a rare disorder that affects the brain. It is part of a group of disorders known as leukodystrophies. Leukodystrophies are diseases that affect the white matter of the brain. The white matter contains nerve fibers (axons), surrounded by a type of sheath or covering called myelin (a fatty, white colored substance) that allows the transmission of impulses or communication among brain cells (neurons). 

LTBL is characterized by changes in specific parts of the brain including the cerebellum, thalamus and brainstem. These changes can be seen by brain imaging exams (MRI). High levels of lactate in the blood and in the cerebral spinal fluid are also seen.[13944][13946][13947]

There are basically two forms of the disease based on severity of symptoms and age of onset: [13946][13947][13948][13949] 

• A mild disease, with onset around 6 months of age, characterized by the loss of acquired skills (psychomotor regression), muscle stiffness (spasticity), irritability and seizures. These symptoms often improve during the toddler years. 
• A severe disease with symptoms that start in newborns and include brain and liver problems. Symptoms generally do not improve with age. 

LTBL is caused by changes (mutations) in the EARS2 gene.[13944][13946] Mutations in this gene decrease the amount of a specific mitochondrial enzyme needed for proper mitochondrial function (mitochondria are cell structures that convert the energy from food into a form that cells can use), and therefore, LTBL is also considered a type of mitochondrial disorder.[13951] It is inherited in an autosomal recessive pattern.[13946] There is still no cure for this disease. Treatment is typically supportive based on presenting symptoms.[13952]

Synonyms

• Combined oxidative phosphorylation defect type 12
• Combined oxidative phosphorylation deficiency 12
• COXPD12
• LTBL
• Leukoencephalopathy-thalamus and brainstem anomalies-high lactate syndrome