SNP Shot: Genomic Insights

Triosephosphate isomerase (TPI) deficiency is a condition characterized by several health issues, including a reduced number of red blood cells (anemia), difficulties with movement, increased vulnerability to infections, and muscle weakness. This muscle weakness can impact breathing and heart function.

The anemia associated with TPI deficiency typically begins in infancy. This specific type of anemia, called hemolytic anemia, is caused by the premature destruction of red blood cells. The resulting shortage of red blood cells, which are responsible for carrying oxygen throughout the body, leads to symptoms like extreme fatigue, pale skin (pallor), and shortness of breath. As red blood cells break down, iron and bilirubin are released into the bloodstream. Individuals with TPI deficiency often have elevated levels of these substances, leading to jaundice, a condition that causes yellowing of the skin and eyes.

Movement problems usually become noticeable around age 2 in individuals with TPI deficiency. These problems are a result of impaired motor neurons, which are specialized nerve cells in the brain and spinal cord responsible for controlling muscle movement. This impairment causes muscle weakness and wasting (atrophy), leading to involuntary muscle tensing (dystonia), tremors, and reduced muscle tone (hypotonia). Seizures may also develop in affected individuals.

Besides the muscles responsible for movement, other muscles can also be affected in TPI deficiency, including the heart (leading to a condition called cardiomyopathy) and the diaphragm (the muscle separating the abdomen and chest). Diaphragm weakness can cause breathing difficulties and can ultimately result in respiratory failure.

People with TPI deficiency are more susceptible to infections due to poorly functioning white blood cells. These cells are part of the immune system and normally identify and attack foreign invaders like viruses and bacteria. Bacterial infections of the respiratory tract are the most common type of infection observed in individuals with TPI deficiency.

Due to respiratory failure, individuals with TPI deficiency often do not survive past childhood. However, in rare cases, individuals with less severe nerve damage or muscle weakness have lived into adulthood.

Inheritance:

TPI deficiency is inherited in an autosomal recessive manner. This means that both copies of the TPI gene in each cell must have mutations for the condition to manifest. Individuals inherit one mutated copy of the gene from each parent. The parents, who each carry only one copy of the mutated gene, are usually asymptomatic (do not exhibit signs or symptoms of the condition).