Case Report: Novel AK2 variant causing reticular dysgenesis with hemophagocytic lymphohistiocytosis-like syndrome and invasive aspergillosis.

BACKGROUND

Reticular dysgenesis (RD) is the most severe form of severe combined immunodeficiency, caused by biallelic AK2 mutations. The association between RD and hemophagocytic lymphohistiocytosis (HLH) remains poorly characterized, with only one prior case reported.

CASE PRESENTATION: A female neonate born to consanguineous parents presented on day 5 of life with fever and profound pancytopenia. Whole-exome sequencing identified a novel homozygous AK2 missense variant (c.79G>C; p.Gly27Arg). The clinical course was complicated by G-CSF-refractory neutropenia, recurrent sepsis, fulminant Aspergillus flavus sinusitis with craniofacial destruction, and HLH-like syndrome (hyperferritinemia 2,258 ng/mL, elevated sCD25 8,450 U/mL). Despite an available HLA-matched sibling donor, hematopoietic stem cell transplantation was precluded by active infection. The patient died at 5 months of age.

CONCLUSION

This is the first report of neonatal RD with concurrent HLH-like syndrome and invasive fungal infection. The novel p.Gly27Arg variant expands the AK2 mutation spectrum. These findings suggest immune dysregulation in RD extends beyond immunodeficiency to include inflammatory dysregulation.