title: Infantile hemophagocytic lymphohistiocytosis in a case of chediak-higashi syndrome caused by a mutation in the LYST/CHS1 gene presenting with delayed umbilical cord detachment and diarrhea.
abstract: A 2-month-old female infant, born to consanguineous parents, presented with infections in skin and upper respiratory tract. She was notable for delayed umbilical cord detachment, partial albinism, and neurological irritability. Giant granules were present in white blood cells. The intracellular perforin content in CD8 T cells seems to correlate to the immune activation state of the patient with 82% and 8% perforin-containing CD8 T cells at active and nonactive hemophagocytic lymphohistiocytosis (HLH) disease, respectively. HLH was confirmed by hemophagocytosis in bone marrow and absent natural killer cell activity. The patient carried a homozygous G>A mutation in the 3' splice site of intron 24 of the LYST/CHS1 gene, leading to the use of an alternative YAG splice site located in exon 25, introducing a premature STOP codon (L2355fsX2370; NP_000072.2). The early-onset accelerated phase in this severe phenotype of Chediak-Higashi syndrome was probably induced by rotaviral infection. Interestingly, the intracellular perforin content in CD8 T cells seems to correlate to the immune activation state of the patient. Late separation of the umbilical cord in concordance with clinical symptoms should lead to evaluation of a possible neutrophil dysfunction including Chediak-Higashi syndrome before onset of HLH.
authors.affiliation: Departments of *Clinical Immunology †Pathology ‡Hans Christian Andersen Children's Hospital, Odense University Hospital, Odense, Denmark.
authors.forename: Christian
authors.initials: C
authors.lastname: Nielsen
authors.forename: Charlotte N
authors.initials: CN
authors.lastname: Agergaard
authors.forename: Marianne A
authors.initials: MA
authors.lastname: Jakobsen
authors.forename: Michael B
authors.initials: MB
authors.lastname: Møller
authors.forename: Niels
authors.initials: N
authors.lastname: Fisker
authors.forename: Torben
authors.initials: T
authors.lastname: Barington
mesh_terms: D002609:Chediak-Higashi Syndrome / Q000150:complications / Q000235:genetics*; D002675:Child, Preschool; D003967:Diarrhea; D005260:Female; D006801:Humans; D051359:Lymphohistiocytosis, Hemophagocytic / Q000209:etiology*; D009154:Mutation / Q000235:genetics*; D011379:Prognosis; D014470:Umbilical Cord / Q000601:surgery*; D033921:Vesicular Transport Proteins / Q000235:genetics*
chemical_list: C102161:LYST protein, human; D033921:Vesicular Transport Proteins