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A novel TCN2 mutation with unusual clinical manifestations of hemolytic crisis and unexplained metabolic acidosis: expanding the genotype and phenotype of transcobalamin II deficiency

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, hepatosplenome...

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Autores principales: Pongphitcha, Pongpak, Sirachainan, Nongnuch, Khongkraparn, Arthaporn, Tim-Aroon, Thipwimol, Songdej, Duantida, Wattanasirichaigoon, Duangrurdee
Formato: Online Artículo Texto
Lenguaje:English
Publicado: BioMed Central 2022
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Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9052601/
https://www.ncbi.nlm.nih.gov/pubmed/35488219
http://dx.doi.org/10.1186/s12887-022-03291-5
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author Pongphitcha, Pongpak
Sirachainan, Nongnuch
Khongkraparn, Arthaporn
Tim-Aroon, Thipwimol
Songdej, Duantida
Wattanasirichaigoon, Duangrurdee
author_facet Pongphitcha, Pongpak
Sirachainan, Nongnuch
Khongkraparn, Arthaporn
Tim-Aroon, Thipwimol
Songdej, Duantida
Wattanasirichaigoon, Duangrurdee
author_sort Pongphitcha, Pongpak
collection PubMed
description 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.
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spelling pubmed-90526012022-04-30 A novel TCN2 mutation with unusual clinical manifestations of hemolytic crisis and unexplained metabolic acidosis: expanding the genotype and phenotype of transcobalamin II deficiency Pongphitcha, Pongpak Sirachainan, Nongnuch Khongkraparn, Arthaporn Tim-Aroon, Thipwimol Songdej, Duantida Wattanasirichaigoon, Duangrurdee BMC Pediatr Case Report 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. BioMed Central 2022-04-29 /pmc/articles/PMC9052601/ /pubmed/35488219 http://dx.doi.org/10.1186/s12887-022-03291-5 Text en © The Author(s) 2022 https://creativecommons.org/licenses/by/4.0/Open AccessThis article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visithttp://creativecommons.org/licenses/by/4.0/ (https://creativecommons.org/licenses/by/4.0/) . The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/ (https://creativecommons.org/publicdomain/zero/1.0/) ) applies to the data made available in this article, unless otherwise stated in a credit line to the data.
spellingShingle Case Report
Pongphitcha, Pongpak
Sirachainan, Nongnuch
Khongkraparn, Arthaporn
Tim-Aroon, Thipwimol
Songdej, Duantida
Wattanasirichaigoon, Duangrurdee
A novel TCN2 mutation with unusual clinical manifestations of hemolytic crisis and unexplained metabolic acidosis: expanding the genotype and phenotype of transcobalamin II deficiency
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
title_full A novel TCN2 mutation with unusual clinical manifestations of hemolytic crisis and unexplained metabolic acidosis: expanding the genotype and phenotype of transcobalamin II deficiency
title_fullStr A novel TCN2 mutation with unusual clinical manifestations of hemolytic crisis and unexplained metabolic acidosis: expanding the genotype and phenotype of transcobalamin II deficiency
title_full_unstemmed A novel TCN2 mutation with unusual clinical manifestations of hemolytic crisis and unexplained metabolic acidosis: expanding the genotype and phenotype of transcobalamin II deficiency
title_short A novel TCN2 mutation with unusual clinical manifestations of hemolytic crisis and unexplained metabolic acidosis: expanding the genotype and phenotype of transcobalamin II deficiency
title_sort novel tcn2 mutation with unusual clinical manifestations of hemolytic crisis and unexplained metabolic acidosis: expanding the genotype and phenotype of transcobalamin ii deficiency
topic Case Report
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9052601/
https://www.ncbi.nlm.nih.gov/pubmed/35488219
http://dx.doi.org/10.1186/s12887-022-03291-5
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