title: Hematopoietic stem cell transplantation of an adolescent with neurological manifestations of homozygous missense PRF1 mutation.
abstract: Individuals with biallelic truncating PRF1 mutations typically present with fulminant early-onset familial hemophagocytic lymphohistiocytosis (FHL). We report a 19-year-old male with a 5-year history of recurrent fever and headaches progressing to refractory seizures. Brain imaging revealed multiple ring enhancing lesions. Laboratory investigations demonstrated that the patient displayed defective lymphocyte cytotoxicity and carried a homozygous missense PRF1 mutation, c.394G > A (p.Gly132Arg). The patient was successfully treated with chemo-immunotherapy followed by matched related allogeneic hematopoietic stem cell transplantation (HSCT). Our findings demonstrate that prompt HSCT of late-onset FHL with primarily neurological manifestation can reverse central nervous system symptoms and improve long-term outcome.
authors.affiliation: Bone Marrow and Stem Cell Transplantation Program, King Hussein Cancer Center, Amman, Jordan.
authors.forename: Ayad Ahmed
authors.initials: AA
authors.lastname: Hussein
authors.forename: Tuka
authors.initials: T
authors.lastname: Hamadah
authors.forename: Monther
authors.initials: M
authors.lastname: Qandeel
authors.forename: Maher
authors.initials: M
authors.lastname: Sughayer
authors.forename: Rula
authors.initials: R
authors.lastname: Amarin
authors.forename: Asem
authors.initials: A
authors.lastname: Mansour
authors.forename: Samuel C
authors.initials: SC
authors.lastname: Chiang
authors.forename: Abdulhadi
authors.initials: A
authors.lastname: Al-Zaben
authors.forename: Marie
authors.initials: M
authors.lastname: Meeths
authors.forename: Yenan T
authors.initials: YT
authors.lastname: Bryceson
mesh_terms: D000293:Adolescent; D058846:Antibodies, Monoclonal, Murine-Derived / Q000627:therapeutic use*; D000970:Antineoplastic Agents / Q000627:therapeutic use*; D001927:Brain Diseases / Q000209:etiology / Q000628:therapy*; D003131:Combined Modality Therapy; D005260:Female; D018380:Hematopoietic Stem Cell Transplantation; D006801:Humans; D051359:Lymphohistiocytosis, Hemophagocytic / Q000150:complications*; D008297:Male; D009154:Mutation / Q000235:genetics*; D054353:Perforin / Q000235:genetics*; D011379:Prognosis; D000069283:Rituximab
chemical_list: D058846:Antibodies, Monoclonal, Murine-Derived; D000970:Antineoplastic Agents; C510468:PRF1 protein, human; D054353:Perforin; D000069283:Rituximab
keywords: HSCT; hemophagocytic lymphohistiocytosis; late onset; primary immunodeficiency