SNP Shot: Genomic Insights

Leukoencephalopathy with thalamus and brainstem involvement and high lactate (LTBL) is a brain disorder classified as a leukodystrophy, a group of genetic conditions affecting the brain's white matter. White matter is composed of nerve fibers insulated by myelin, a fatty substance crucial for rapid nerve impulse transmission. In leukodystrophies, the white matter is abnormal.

LTBL is characterized by specific brain changes detectable through magnetic resonance imaging (MRI). These changes predominantly affect white matter in the cerebrum and cerebellum. The brainstem, connecting the brain to the spinal cord, along with structures like the thalamus, midbrain, pons, and medulla oblongata, may also show abnormalities. Furthermore, thinning of the corpus callosum, the tissue connecting the brain's hemispheres, is common. Elevated levels of lactate, a chemical compound, are also typically found in the brain and body of individuals with LTBL.

The severity of LTBL varies significantly. Individuals with milder forms usually exhibit symptoms after 6 months of age, including loss of mental and motor skills (psychomotor regression), muscle stiffness (spasticity), and marked irritability. Some may experience seizures. However, after the age of 2, improvements are often observed. Children may regain some motor and cognitive abilities, seizures may diminish or disappear, MRI scans may appear more normal, and lactate levels may decrease.

In severe cases of LTBL, symptoms appear shortly after birth. Affected infants typically exhibit delayed development of mental and motor skills (psychomotor delay), low muscle tone (hypotonia), involuntary muscle contractions (dystonia), muscle spasticity, and seizures. Some experience extremely elevated lactate levels (lactic acidosis), leading to severe respiratory issues and abnormal heart rhythms. Liver failure can also occur. In severe cases, these symptoms do not improve and can be life-threatening. Some individuals with LTBL present with features that fall between the mild and severe ends of the spectrum.

Inheritance:

LTBL follows an autosomal recessive inheritance pattern. This means that for an individual to be affected, they must inherit a mutated copy of the relevant gene from both parents. Parents who each carry one copy of the mutated gene are typically unaffected carriers of the condition.