Leukoencephalopathy with thalamus and brainstem involvement and high lactate

Alternate names

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

Definition

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.

Summary

• 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).

Cause

• LTBL is caused by changes (mutations) in the EARS2 gene.
• 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.

Inheritance

Autosomal recessive inheritance, a 25% chance

It is inherited in an autosomal recessive pattern.

Forms

There are basically two forms of the disease based on severity of symptoms and age of onset: 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.
• The severity of the condition varies.
• Mildly affected individuals usually develop signs and symptoms after the age of 6 months.
• Loss of mental and movement abilities (psychomotor regression), muscle stiffness (spasticity), and extreme irritability are common, and some people with mild LTBL develop seizures.
• However, after age 2, the signs and symptoms of the condition improve: affected children regain some psychomotor abilities, seizures are reduced or disappear, MRI results become more normal, and lactate levels drop.

Signs and symptoms

• The severity of the condition varies.
• Mildly affected individuals usually develop signs and symptoms after the age of 6 months.
• Loss of mental and movement abilities (psychomotor regression), muscle stiffness (spasticity), and extreme irritability are common, and some people with mild LTBL develop seizures.
• However, after age 2, the signs and symptoms of the condition improve: affected children regain some psychomotor abilities, seizures are reduced or disappear, MRI results become more normal, and lactate levels drop.
• Severely affected individuals have features that begin soon after birth.
• These infants typically have delayed development of mental and movement abilities (psychomotor delay), weak muscle tone (hypotonia), involuntary muscle tensing (dystonia), muscle spasticity, and seizures.
• Some have extremely high levels of lactate (lactic acidosis), which can cause serious breathing problems and an abnormal heartbeat.
• Liver failure occurs in some severely affected infants.
• In severe cases, the signs and symptoms do not improve and can be life-threatening.
• In some people with LTBL, the features fall between mild and severe.

Diagnosis

• 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.

Treatment

• There is still no cure for this disease.
• Treatment is typically supportive based on presenting symptoms.

NIH genetic and rare disease info

• NIH info on Leukoencephalopathy with thalamus and brainstem involvement and high lactate

Leukoencephalopathy with thalamus and brainstem involvement and high lactate is a rare disease.

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