Masquerading as lymphoma: the accelerated phase of Chediak–Higashi syndrome and its novel mutation

Abstract

Chediak-Higashi syndrome (CHS) is a rare autosomal recessive disorder. The clinical presentation may be fatal if these patients develop the catastrophic accelerated phase, i.e., hemophagocytic lymphohistiocytosis (HLH). We report a 2.5-year boy that presented to us with complaints of fever, recurrent cough, glandular neck swelling, and abdominal distension for 6 months. He also had a history of female sibling death (age, 3 years) 3 years ago with similar complaints. On examination, he had light skin and silver hair along with severe pallor, generalized significant lymphadenopathy, severe acute malnutrition, and hepatosplenomegaly. Since the patient’s peripheral blood smear and bone marrow showed giant primary azurophilic granules in lymphocytes and eosinophils and the presence of 5 out of 8 HLH 2004 criteria, i.e., fever, hepatosplenomegaly, pancytopenia, hyperferritinemia, and hypertriglyceridemia, a diagnosis of CHS with HLH was made. However, no hemophagocytosis was observed. A novel homozygous nonsense variant in exon 45 of the LYST gene (chr1:g.235702929G > A) similar to the one found in the elder female sibling and previously reported “likely pathogenic” was discovered, which was identified through genetic testing. This case highlights the importance of genetic testing in diagnosis as well as antenatal counselling. © The Author(s), under exclusive licence to Institute of Plant Genetics Polish Academy of Sciences 2025.