title: A novel mutation of the transcobalamin II gene in an infant presenting with hemophagocytic lymphohistiocytosis.
abstract: Transcobalamin II (TC II) deficiency is a rare disorder of cobalamin (CBL, vitamin B12) metabolism that occurs due to mutations in transcobalamin gene (TCN2). Hemophagocytic lymphohistiocytosis (HLH) in contrast is a syndrome characterized by uncontrolled immune response with hyperinflammation. A 2-month-old male baby was admitted with complaints of fever, cough, diarrhea, and respiratory distress. The parents were first cousins. The baby exhibited five of the eight diagnostic criteria for HLH-2004 and was diagnosed as HLH. A second bone marrow aspiration demonstrated megaloblastic changes in the erythroid series. The patient's vitamin B12 level was normal; however, hyperhomocysteinemia was present. A genetic deficiency of TC II was suspected. The patient and his parents were tested for TCN2 mutation. He had a homozygote mutation that was not included in Human 'Gene Mutation Database Cardiff'. The patient was treated with intramuscular vitamin B12, which was followed by improvement in both clinical and laboratory findings. He was 12 months old at the time of this report, with normal physical and neuromotor development. In this case presenting with the clinical and laboratory findings of HLH, TC II deficiency was diagnosed. A new mutation was found that was not reported before. Potential causative mechanisms of HLH induced by defects of cobalamin synthesis merit further investigation.
authors.affiliation: Hematology Unit, Department of Pediatrics, Faculty of Medicine, Mersin University, Mersin, Turkey, unalselma@hotmail.com.
authors.forename: Selma
authors.initials: S
authors.lastname: Unal
authors.forename: Ozlem
authors.initials: O
authors.lastname: Tezol
authors.forename: Yesim
authors.initials: Y
authors.lastname: Oztas
mesh_terms: D002872:Chromosome Deletion; D002892:Chromosomes, Human, Pair 22; D056426:Genetic Loci; D006579:Heterozygote; D006801:Humans; D007223:Infant; D051359:Lymphohistiocytosis, Hemophagocytic / Q000175:diagnosis / Q000188:drug therapy / Q000235:genetics*; D008297:Male; D009154:Mutation; D014155:Transcobalamins / Q000235:genetics*; D016896:Treatment Outcome; D014805:Vitamin B 12 / Q000627:therapeutic use
chemical_list: D014155:Transcobalamins; D014805:Vitamin B 12