Myelodysplasia uncovering transcobalamin deficiency

Transcobalamin deficiency is an autosomal recessive disease caused by pathogenic variants in the TCN2 gene. It is a multisystem disorder, with haematological manifestations such as megaloblastic anaemia and pancytopenia. Neurological manifestations include ataxia, hypotonia and neuropathy. Gastrointestinal and immunological clinical presentations include diarrhoea, cytomegalovirus (CMV) colitis, failure to thrive and recurrent infections.We report a female toddler who initially presented at early infancy with severe failure to thrive, diarrhoea, CMV colitis and pancytopenia and was initially diagnosed with childhood myelodysplastic syndrome based on bone marrow examination and a strong family history in her cousins. Whole exome sequencing revealed a homozygous pathogenic variant, c.927_930del (p.(Cys309Trpfs*50)), in the TCN2, consistent with a diagnosis of autosomal recessive transcobalamin deficiency. Treatment with parenteral hydroxocobalamin resulted in dramatic improvement in her symptoms and resolved the myelodysplastic changes.