IDH1 mutated acute myeloid leukemia in a child with metaphyseal chondromatosis with D-2-hydroxyglutaric aciduria

Pediatr Hematol Oncol. 2020 Aug;37(5):431-437. doi: 10.1080/08880018.2020.1737284. Epub 2020 Mar 13.


D-2-hydroxyglutaric aciduria (D-2-HGA) is a rare metabolic disorder characterized by developmental delay, hypotonia, and bi-allelic mutations in D-2-hydroxyglutarate dehydrogenase (D2HGDH) or a single gain-of-function mutation in isocitrate dehydrogenase 2 (IDH2). Metaphyseal chondromatosis with D-2-hydroxyglutaric aciduria (MC-HGA) is a type of D-2-HGA that has been previously reported in ten patients (OMIM 614875), three of whom had somatic mosaicism for R132 variants in isocitrate dehydrogenase 1 (IDH1). We describe a 3-year-old boy with MC-HGA who subsequently developed acute myeloid leukemia (AML) and was found to have an IDH1 R132C mutation in a leukemic bone marrow sample. Further testing revealed presence of somatic mosaicism for IDH1 R132C variant, suggesting an association of IDH1 in inducing myeloid leukemogenesis.

Keywords: AML; IDH1 mutation; MC-HGA.

Publication types

  • Case Reports

MeSH terms

  • Antineoplastic Combined Chemotherapy Protocols / therapeutic use
  • Brain Diseases, Metabolic, Inborn / complications
  • Brain Diseases, Metabolic, Inborn / genetics*
  • Child, Preschool
  • Chondromatosis / complications
  • Chondromatosis / drug therapy
  • Chondromatosis / genetics*
  • Hematopoietic Stem Cell Transplantation
  • Humans
  • Isocitrate Dehydrogenase / genetics*
  • Leukemia, Myeloid, Acute / complications
  • Leukemia, Myeloid, Acute / drug therapy
  • Leukemia, Myeloid, Acute / genetics*
  • Male
  • Mutation
  • Treatment Outcome


  • Isocitrate Dehydrogenase
  • IDH1 protein, human

Supplementary concepts

  • 2-Hydroxyglutaricaciduria