Triosephosphate isomerase deficiency (Triosephosphate isomerase deficiency) - Gen TPI1.

Triosephosphate isomerase deficiency is a disease characterized by anemia, impaired movement, increased susceptibility to infections, and muscle weakness that can affect breathing and heart function.

In this disease, hemolytic anemia begins in childhood and leads to tiredness, paleness and shortness of breath. These individuals have an excess of iron and bilirubin in the peripheral blood, causing jaundice. For its part, the movement problems usually become apparent at 2 years of age in people with deficient triosephosphate and are due to the deterioration of motor neurons. This deficiency leads to atrophy and other movement problems typical of the disease, including dystonia, tremor, hypotonia and seizures. In addition, people with triosephosphate deficiency are at increased risk of developing most common bacterial infections of the respiratory tract. The weakness of other muscles, such as the heart and diaphragm can lead to respiratory problems, and ultimately to respiratory failure.

These individuals often do not survive beyond infancy due to respiratory failure. In some rare cases, affected individuals without deep nerve damage or muscle weakness have lived to adulthood.

This process is due to mutations in the TPI1 gene, located on the short arm of chromosome 12 (12p13). This gene encodes the enzyme triosephosphate 1. This enzyme is involved in the process of glycolysis. During glycolysis, glucose is broken down to produce energy for cells. Triosephosphate isomerase enzyme the 1 performs a specific reaction during glycolysis: the conversion of dihydroxyacetone phosphate molecule (DHAP) to glyceraldehyde 3-phosphate. This conversion can go both ways, which means that the enzyme can also convert back glyceraldehyde 3-phosphate in DHAP. Other additional steps become glyceraldehyde 3-phosphate into other molecules that ultimately produce energy as a molecule called ATP. For triosephosphate isomerase 1 enzyme is active, it must bind to another enzyme triosephosphate 1, forming a complex of two enzymes called dimer.

They have identified at least 12 mutations in the TPI1 gene in people with deficient triosephosphate. These mutations may lead to encoding an enzyme with reduced function. Consequently, glycolysis deteriorates and the cells have a decreased power supply. A mutation of the TPI1 gene is responsible for about 80% of cases triosephosphate deficiency. This change replaces glutamic acid amino acid with the amino acid aspartic acid at position 104 in the triosephosphate isomerase enzyme 1 (Glu104Asp or E104D). This mutation causes instability of the enzyme and impairs their ability to form a dimer and become active. In addition, red blood cells depend solely on the breakdown of glucose for energy. No functional enzyme triosephosphate 1 to convert DHAP to glyceraldehyde 3-phosphate, DHAP accumulate erythrocytes, which is toxic at high concentrations. Unlike other cells, erythrocytes have no alternative pathways to decompose DHAP. Due to the accumulation of DHAP and lack of cellular energy, erythrocytes die earlier than normal.

Cells with high energy demands, as nerve cells in the brain, white blood cells and heart muscle cells are also susceptible to cell death due to energy reduction caused by the alteration of glycolysis. Nerve cells in the cerebellum are particularly affected in people with this disease. Death of red and white blood cells, nerve cells in the brain and heart muscle cells leads to the signs and symptoms of deficiency triosephosphate.

This disease is inherited in an autosomal recessive pattern, which means that both copies of the gene in every cell must have mutations for alteration is expressed. The parents of an individual with an autosomal recessive disease have a copy of the mutated gene, but usually show no signs and symptoms of the disease.

Tests in IVAMI: in IVAMI perform detection of mutations associated with deficiency triosephosphate by complete PCR amplification of the exons of the TPI1 gene, and subsequent sequencing.

Samples recommended: EDTA blood collected for separation of blood leukocytes, or impregnated sample card with dried blood (IVAMI may mail the card to deposit the blood sample).