title: Partial albinism with immunodeficiency (Griscelli syndrome).
abstract: Partial albinism with immunodeficiency is a rare and fatal immunologic disorder characterized by pigmentary dilution and variable cellular immunodeficiency. To define the phenotype, therapy, and outcome, we retrospectively analyzed seven consecutive patients. Primary abnormalities included a silvery-grayish sheen to the hair, large pigment agglomerations in hair shafts, and an abundance of mature melanosomes in melanocytes, with reduced pigmentation of adjacent keratinocytes. Clinical onset occurred between the ages of 4 months and 4 years and was characterized by accelerated phases (lymphohistiocytic infiltration of multiple organs, including the brain and the meninges), triggered by viral and bacterial infections. Characteristic laboratory features included pancytopenia, hypofibrinogenemia, hypertriglyceridemia, and hypoproteinemia. Consistent immunologic abnormalities were characterized by absent delayed-type cutaneous hypersensitivity and impaired natural killer cell function. Some patients had secondary hypogammaglobulinemia, impaired major histocompatibility complex-mediated cytotoxic effects, a decreased capacity of lymphocytes to trigger a mixed lymphocyte reaction, or various functional granulocytic abnormalities. The disease seems to be invariably lethal without bone marrow transplantation; the mean age at the time of death was 5 years. Bone marrow transplantation has been performed in three cases; two patients died in the immediate posttransplantation period of infectious complications, but one patient is cured after a follow-up of 5 years. We conclude that partial albinism with immunodeficiency (Griscelli syndrome) can be differentiated from Chédiak-Higashi syndrome by pathognomonic histologic features. One of the underlying immunologic defects may be a defective function of natural killer cells, predisposing the patient to virus-associated hemophagocytic syndrome or accelerated phases. The prognosis is very poor unless early bone marrow transplantation is carried out.
authors.affiliation: Unité d'Immunologie et d'Hématologie, INSERM Unité 132, Paris, France.
authors.forename: C
authors.initials: C
authors.lastname: Klein
authors.forename: N
authors.initials: N
authors.lastname: Philippe
authors.forename: F
authors.initials: F
authors.lastname: Le Deist
authors.forename: S
authors.initials: S
authors.lastname: Fraitag
authors.forename: C
authors.initials: C
authors.lastname: Prost
authors.forename: A
authors.initials: A
authors.lastname: Durandy
authors.forename: A
authors.initials: A
authors.lastname: Fischer
authors.forename: C
authors.initials: C
authors.lastname: Griscelli
mesh_terms: D000305:Adrenal Cortex Hormones / Q000627:therapeutic use; D000417:Albinism / Q000150:complications* / Q000175:diagnosis / Q000235:genetics / Q000276:immunology / Q000628:therapy; D016026:Bone Marrow Transplantation; D002493:Central Nervous System Diseases / Q000209:etiology; D002675:Child, Preschool; D003131:Combined Modality Therapy; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D006968:Hypersensitivity, Delayed / Q000276:immunology; D007111:Immunity, Cellular; D007153:Immunologic Deficiency Syndromes / Q000150:complications* / Q000175:diagnosis / Q000235:genetics / Q000276:immunology / Q000628:therapy; D007165:Immunosuppression Therapy; D007223:Infant; D007239:Infections / Q000209:etiology; D007694:Killer Cells, Natural / Q000276:immunology; D008297:Male; D010641:Phenotype; D012008:Recurrence; D012189:Retrospective Studies; D016896:Treatment Outcome
chemical_list: D000305:Adrenal Cortex Hormones