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Leukoencephalopathy with thalamus and brainstem involvement and high lactate
Reviewed by Medicinsk Expert•Last updated: 2026-10-22•Condition

Leukoencephalopathy with thalamus and brainstem involvement and high lactate

This rare genetic leukodystrophy affects the nervous system's white matter and is characterized by distinct brain abnormalities and elevated lactate levels.

Overview

Leukoencephalopathy with thalamus and brainstem involvement and high lactate (LTBL) is a genetic disorder belonging to a group of conditions called leukodystrophies. These disorders affect the white matter of the nervous system, which consists of nerve fibers insulated by a fatty substance called myelin that promotes the transmission of nerve impulses.

Brain Abnormalities

LTBL is identified through magnetic resonance imaging (MRI) showing distinct changes in the brain, including:

  • Abnormalities in the white matter of the cerebrum and cerebellum.
  • Involvement of the brainstem, including the thalamus, midbrain, pons, and medulla oblongata.
  • Thinning of the corpus callosum, the tissue connecting the two halves of the brain.
  • High levels of lactate in the brain and body.

Clinical Severity

The severity of LTBL varies significantly:

  • Mild cases: Symptoms often appear after 6 months of age, including psychomotor regression, spasticity, and irritability. After age 2, symptoms often improve, and lactate levels may drop.
  • Severe cases: Features begin shortly after birth, including psychomotor delay, hypotonia, dystonia, seizures, and potentially life-threatening lactic acidosis or liver failure.

Causes

LTBL is caused by mutations in the EARS2 gene, which provides instructions for making the enzyme mitochondrial glutamyl-tRNA synthetase. This enzyme is essential for protein synthesis within mitochondria, the energy-producing centers of cells. Mutations in this gene hinder the addition of the amino acid glutamate to mitochondrial proteins, which is thought to disrupt mitochondrial energy production.

Inheritance

This condition is inherited in an autosomal recessive pattern, meaning both copies of the EARS2 gene in each cell must have mutations for the disorder to occur. Parents of an affected individual typically carry one mutated copy but do not show symptoms.

Frequently Asked Questions

During acute intercurrent infections or metabolic stress, children with LTBL require urgent medical support to mitigate severe lactic acidosis. Management focuses on aggressive hydration, continuous intravenous dextrose infusions to suppress catabolic cellular breakdown, close monitoring of serum electrolytes and blood gas parameters, prompt treatment of underlying infections, and avoiding medications or mitochondrial toxins that impede respiratory chain function.
Proton magnetic resonance spectroscopy (H-MRS) provides key diagnostic evidence by revealing a prominent lactate peak within affected brain regions, including the cerebral white matter, thalamus, and brainstem. When paired with standard MRI showing selective deep white matter abnormalities, corpus callosum thinning, and sparing of the subcortical U-fibers, this elevated brain lactate signature strongly suggests LTBL and directs targeted EARS2 genetic testing.
Because LTBL is inherited in an autosomal recessive manner, parents of an affected child are typically asymptomatic obligate carriers of a pathogenic EARS2 variant. With each subsequent pregnancy, there is a 25% chance that the child will inherit both mutated gene copies and be affected, a 50% chance the child will be an asymptomatic carrier, and a 25% chance the child will inherit two normal alleles. Carrier testing, prenatal diagnosis, or preimplantation genetic testing can assist with family planning.
In the milder or biphasic form of LTBL, children typically experience motor and developmental regression between 6 and 24 months, followed by a stabilization phase and gradual recovery of motor milestones. While the precise mechanism is still being investigated, this improvement is thought to reflect developmental maturation of the central nervous system, compensatory mitochondrial protein synthesis, and shifting metabolic demands as brain myelination progresses beyond early infancy.
Source: MedlinePlus, National Library of Medicine

MedlinePlus brings together authoritative health information from the National Library of Medicine (NLM), the National Institutes of Health (NIH), and other government agencies and health-related organizations.

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