Reticular dysgenesis exacerbated by hemophagocytic lymphohistiocytosis and the presence of unusual histiocyte-like cells in bone marrow

Immunobiology. 2021 Nov;226(6):152143. doi: 10.1016/j.imbio.2021.152143. Epub 2021 Sep 24.


We report a rare case of agranulocytosis and lymphopenia complicated with hemophagocytic lymphohistiocytosis. Diagnosis of reticular dysgenesis was made by detection of a pathogenic stop gain variant in the AK2 gene on targeted next generation sequencing and confirmed by Sanger sequencing. Parents were found to be carriers for this variant. Bone marrow aspirate and biopsy was also performed with a clinical diagnosis of severe combined immunodeficiency with HLH. However, no hemophagocytosis was noted in the bone marrow aspirate or trephine biopsy. Instead, it showed aggregates of large histiocyte-like cells, scattered erythroid precursors and megakaryocytes. These cells were confused to be some form of storage cells, but did not resemble storage cells seen in Gaucher's disease or Niemann Pick disease. Myeloid precursors were very few in number. Reticular dysgenesis was not suspected during admission due to a lack of awareness of this entity. Testing for sensorineural deafness in neonates with severe agranulocytosis and lymphopenia would facilitate an early diagnosis of reticular dysgenesis. To the best of our knowledge, hemophagocytic lymphohistiocytosis has not been previously reported in association with reticular dysgenesis.

Keywords: AK2 gene; ATP; Reticular dysgenesis; Sensorineural deafness; Severe combined immunodeficiency; Severe leucopenia.

Publication types

  • Case Reports

MeSH terms

  • Adenylate Kinase / genetics
  • Biomarkers
  • Biopsy
  • Bone Marrow / pathology*
  • Bone Marrow Cells / pathology
  • DNA Mutational Analysis
  • Disease Management
  • Disease Susceptibility
  • Hematologic Tests
  • Histiocytes / pathology*
  • Humans
  • Infant
  • Leukopenia / diagnosis*
  • Leukopenia / etiology*
  • Lymphohistiocytosis, Hemophagocytic / complications*
  • Lymphohistiocytosis, Hemophagocytic / diagnosis*
  • Male
  • Mutation
  • Phenotype
  • Severe Combined Immunodeficiency / diagnosis*
  • Severe Combined Immunodeficiency / etiology*
  • Severity of Illness Index


  • Biomarkers
  • Adenylate Kinase
  • adenylate kinase 2

Supplementary concepts

  • Reticular dysgenesis