Transcobalamin deficiency

Transcobalamin deficiency (also known as transcobalamin II deficiency or TC II deficiency) is a rare autosomal recessive disorder affecting the transport of vitamin B12 (cobalamin) in the body. Transcobalamin II is the primary transport protein responsible for delivering cobalamin from the intestine and bloodstream to cells throughout the body. When this protein is absent or dysfunctional due to mutations in the TCN2 gene, cells cannot adequately take up cobalamin, leading to intracellular cobalamin depletion despite sometimes normal serum vitamin B12 levels. The condition typically presents in early infancy, usually within the first few months of life, with severe megaloblastic anemia, pancytopenia, failure to thrive, vomiting, diarrhea, and weakness. Neurological manifestations can develop if the condition is not promptly treated and may include developmental delay, hypotonia, seizures, and progressive neurological deterioration. The immune system may also be affected, with some patients exhibiting immunodeficiency and increased susceptibility to infections, including agammaglobulinemia or hypogammaglobulinemia. Early diagnosis and treatment are critical to prevent irreversible neurological damage. Treatment consists of high-dose intramuscular or parenteral hydroxocobalamin (vitamin B12) injections, which bypass the defective transport system and allow sufficient cobalamin to enter cells through passive diffusion. With early and sustained treatment, hematological abnormalities typically resolve rapidly, and neurological outcomes can be favorable. Lifelong supplementation is required, and regular monitoring of hematological parameters, metabolic markers (such as methylmalonic acid and homocysteine levels), and neurological development is essential for optimal management.

Common questions about Transcobalamin deficiency