Work

Fatal accelerated-phase Chediak-Higashi syndrome caused by an in-frame LYST deletion: first documented case from Syria

Year: 2026

Type: article

Abstract: Chediak-Higashi Syndrome (CHS) is a very rare genetic disorder that follows an autosomal recessive inheritance pattern. Biallelic mutations in the lysosomal trafficking regulator ( LYST ) gene cause abnormal granule formation, leading to clinical manifestations including organomegaly, immunodeficiency, and neurological dysfunction. A 9-year-old girl presented with a one-month history of fever, abdominal distension and jaundice. She had massive hepatosplenomegaly, pancytopenia, cholestatic liver dysfunction and a prolonged prothrombin time; infectious work-up was negative and duodenal biopsy showed coeliac disease. An older sister had died at the same age and had a history of splenomegaly that had not been investigated. She was discharged after splenectomy but returned two months later with left-sided ptosis and esotropia associated with a sphenoid sinus abscess, alongside recurrent dental abscesses, epistaxis and peripheral fundus hypopigmentation. Despite treatment with antibiotics and corticosteroids and supportive blood transfusions, she developed multiple intracranial abscesses, recurrent pancytopenia and marrow features of myelodysplastic syndrome. Genetic testing identified a homozygous in-frame nine-base-pair deletion in the LYST gene, c.7029_7037delATCACCAGC, p.(Ser2344_Ala2346del), in exon 24. This variant had previously been reported as possibly disease-causing but was classified as a variant of uncertain significance in the current report. She died from gastrointestinal bleeding before transplantation could be arranged. CHS is a rare, potentially life-threatening disorder. genetic testing can complement clinical and hematological findings and help establish the diagnosis. This case highlights the importance of considering CHS in children presenting with recurrent infections, hepatosplenomegaly, and hematological abnormalities. Not applicable.

Source: BMC Pediatrics

DOI: 10.1186/s12887-026-07971-4