Triose phosphate-isomerase deficiency

Triose phosphate isomerase (TPI) deficiency is an extremely rare and severe autosomal recessive metabolic disorder caused by mutations in the TPI1 gene located on chromosome 12p13. TPI is a key enzyme in the glycolytic pathway, and its deficiency affects multiple organ systems, most notably the blood, nervous system, and skeletal muscle. The disease is considered one of the most severe glycolytic enzymopathies. It is also known as TPI deficiency or triose phosphate isomerase deficiency hemolytic anemia. Clinical features typically manifest in infancy and include chronic hemolytic anemia (due to premature destruction of red blood cells), progressive neuromuscular dysfunction, increased susceptibility to infections, and cardiomyopathy. Neurological involvement is a hallmark of the disease and distinguishes it from other red cell enzymopathies; affected children often develop progressive spasticity, dystonia, and lower motor neuron degeneration resembling spinal muscular atrophy. Severe hypotonia and developmental regression are common. Many patients experience recurrent bacterial infections due to impaired white blood cell function. The prognosis is generally poor, with most affected individuals dying in early childhood, often before the age of five, typically from respiratory infections or cardiac failure. There is currently no curative treatment for TPI deficiency. Management is supportive and may include blood transfusions for severe anemia, infection prevention and treatment, and physical therapy. Splenectomy has been performed in some cases to reduce hemolysis but does not alter the neurological progression. Research into potential therapies is ongoing but limited by the extreme rarity of the condition.

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