A novel TCN2 mutation with unusual clinical manifestations of hemolytic crisis and unexplained metabolic acidosis: expanding the genotype and phenotype of transcobalamin II deficiency
Issued Date
2022-12-01
Resource Type
eISSN
14712431
Scopus ID
2-s2.0-85128920429
Pubmed ID
35488219
Journal Title
BMC Pediatrics
Volume
22
Issue
1
Rights Holder(s)
SCOPUS
Bibliographic Citation
BMC Pediatrics Vol.22 No.1 (2022)
Suggested Citation
Pongphitcha P., Sirachainan N., Khongkraparn A., Tim-Aroon T., Songdej D., Wattanasirichaigoon D. A novel TCN2 mutation with unusual clinical manifestations of hemolytic crisis and unexplained metabolic acidosis: expanding the genotype and phenotype of transcobalamin II deficiency. BMC Pediatrics Vol.22 No.1 (2022). doi:10.1186/s12887-022-03291-5 Retrieved from: https://repository.li.mahidol.ac.th/handle/20.500.14594/85319
Title
A novel TCN2 mutation with unusual clinical manifestations of hemolytic crisis and unexplained metabolic acidosis: expanding the genotype and phenotype of transcobalamin II deficiency
Author's Affiliation
Other Contributor(s)
Abstract
Background: Transcobalamin deficiency is a rare inborn metabolic disorder, characterized by pancytopenia, megaloblastic anemia, failure to thrive, diarrhea, and psychomotor retardation. Case presentation: We describe a patient who first presented at 3 months of age, with pancytopenia, hepatosplenomegaly, recurrent infection, metabolic acidosis, and acute hemolytic crisis. Extensive hematologic and immunologic investigations did not identify inherited bone marrow failure syndrome, acute leukemia or its related disorders. Whole exome sequencing identified a novel homozygous TCN2 mutation, c.428-2A > G and mRNA study confirmed an aberrant transcription of exon 4 skipping. The mutant protein is predicted to have an in-fame 51 amino acids deletion (NP_000346:p.Gly143_Val193del). The patient exhibited marked clinical improvement following hydroxocobalamin treatment. Conclusions: Transcobalamin deficiency should be investigated in infants with unexplained pancytopenia and acute hemolytic crisis with or without typical evidence of vitamin B12 deficiency.