[Inherited transcobalamin-II-deficiency: clinical, genetic studies and diagnosis using cultured fibroblasts]

A boy born healthy, developed gastrointestinal symptoms (diarrhea, vomiting, ulcerative stomatitis) and megaloblastic anaemia with thrombocytopenia and neutropenia at the age of five weeks. Serum levels of folate and cobalamin were normal, but there was cobalamin-mal absorption. In his serum apo-TC2 was not detectable and immunoreactive total TC2 was very low (10% of normal values). Cultured skin fibroblasts failed to secrete functioning TC2. Pharmacological amounts of parenteral Cyanocobalamin, administered regularly, led to hematological remission and normal development. Interruption of therapy was followed by relapse within a few weeks. A coexisting hypogammaglobulinemia did not respond to cobalamin therapy at the selected dose level. A family investigation of serum TC2 concentrations and the genetic TC2 variants in 7 persons of three generations yielded evidence of autosomal-recessive inheritance of a silent TC2 allele (TC2 QLFL SEA-like). Three persons with heterozygous deficiency were asymptomatic.