Triose phosphate-isomerase deficiency

=Triose Phosphate Isomerase Deficiency = Triose Phosphate Isomerase Deficiency (TPI deficiency) is a rare autosomal recessive metabolic disorder that affects the glycolytic pathway. It is characterized by a deficiency in the enzyme triose phosphate isomerase, which is crucial for the proper metabolism of carbohydrates.

Pathophysiology

Triose phosphate isomerase (TPI) is an enzyme that catalyzes the reversible conversion of dihydroxyacetone phosphate (DHAP) to glyceraldehyde-3-phosphate (G3P) in the glycolytic pathway. This step is essential for efficient energy production in cells. In TPI deficiency, mutations in the TPI1 gene lead to reduced or absent enzyme activity, resulting in the accumulation of DHAP and a decrease in G3P levels. This imbalance disrupts normal cellular metabolism and energy production.

Clinical Features

Patients with TPI deficiency typically present with a range of symptoms, including:

• Hemolytic anemia
• Neurological dysfunction
• Cardiomyopathy
• Muscle weakness

The severity of symptoms can vary, but the condition is often life-threatening, with many affected individuals not surviving past early childhood.

Diagnosis

Diagnosis of TPI deficiency is based on clinical presentation, biochemical analysis, and genetic testing. Key diagnostic features include:

• Elevated levels of DHAP in blood and urine
• Reduced TPI enzyme activity in red blood cells
• Identification of mutations in the TPI1 gene through genetic testing

Treatment

Currently, there is no cure for TPI deficiency. Treatment is primarily supportive and focuses on managing symptoms. This may include:

• Blood transfusions for anemia
• Physical therapy for muscle weakness
• Nutritional support

Research into potential therapies, such as enzyme replacement or gene therapy, is ongoing.

Genetics

TPI deficiency is inherited in an autosomal recessive manner. This means that an affected individual must inherit two copies of the mutated TPI1 gene, one from each parent. Carriers, who have one normal and one mutated gene, typically do not show symptoms.

Epidemiology

TPI deficiency is extremely rare, with only a few dozen cases reported worldwide. It affects both males and females equally and has been identified in various ethnic groups.

Research Directions

Ongoing research is focused on understanding the molecular mechanisms of TPI deficiency and developing potential treatments. Areas of interest include:

• Gene therapy approaches to correct the underlying genetic defect
• Small molecule drugs to enhance residual enzyme activity
• Stem cell therapy to replace damaged tissues

See Also

• Glycolysis
• Metabolic disorders
• Enzyme deficiencies

NIH genetic and rare disease info

• NIH info on Triose phosphate-isomerase deficiency

Triose phosphate-isomerase deficiency is a rare disease.