Towards the targeted management of Chediak-Higashi syndrome

Abstract

Chediak-Higashi syndrome (CHS) is a rare, autosomal recessive congenital immunodeficiency caused by mutations in CHS1, a gene encoding a putative lysosomal trafficking protein. In the majority of patients, this disorder is typically characterized by infantile-onset hemophagocytic lymphohistiocytosis (HLH), which is lethal unless allogeneic transplantation is performed. A small number of individuals have the attenuated form of the disease and do not benefit from transplant. Improved outcomes of transplantation have been reported when performed before the development of HLH, thus it is important to quickly differentiate patients that present with the childhood form of disease and to prematurely enroll them into a transplantation protocol. In addition, this would also preclude those that exhibit clinical phenotypes of adolescent and adult CHS from this treatment. Patients with an absence of cytotoxic T lymphocyte (CTL) function have a high risk for developing HLH, and could therefore benefit the most from early hematopoietic stem cell transplantation (HSCT). However, although normal CTL cytotoxicity or bi-allelic missense mutations do not exclude the occurrence of HLH in childhood, a more conservative approach is justified. This article summarizes recent advances in the clinical characterization of CHS patients, provides updates on promising new testing methods, and focuses on specific therapeutic approaches.

Association of Chediak-Higashi Syndrome and Human Immunodeficiency Virus Type 1 Acute Infection

“…Platelets are also functionally defective with reduced dense granules and impaired 36 ( blood cells defects reported in CHS [11] including neutropenia and thrombocytopenia, consistent with the initial clinical symptoms, such as fever and a penile infectious and bleeding lesion. Moreover, the production of anti-HIV antibodies was not impaired in this patient, as reported previously [12]. The HIV-1 infection reported in this study fits in stage IV [6,7], which is characterized by positive detection tests of RNA-HIV, p24 antigen, and anti-HIV antibodies using rapid and serological tests.…”

“…functions. Immunoglobulin levels and complement are generally normal [12]. The natural history and pathogenic processes of HIV-1 infection are complex.…”

Lysosomal Trafficking Regulator (LYST)

“…The first case of Chediak-Higashi syndrome (CHS) was reported in 1943 (Lozano et al 2014). The disease is very rare, with less than 500 cases reported worldwide in the past 20 years (Kaplan et al 2008).…”

“…The disease is very rare, with less than 500 cases reported worldwide in the past 20 years (Kaplan et al 2008). Most patients with CHS (85 -90 %) are diagnosed in early childhood with severe clinical manifestations, including variable degrees of oculocutaneous albinism and recurrent fatal pyogenic infections (Kaplan et al 2008;Lozano et al 2014). Hair color may be blond, gray, or white, often with a distinguishing silvery or metallic sheen (Lozano et al 2014).…”

Sodobni pristop za diagnosticiranje prirojenih motenj delovanja trombocitov

“…Aspirin--like defects) (16), motnje skladiščenja substanc (angl. "storage-pool" disease) v gostih trombocitnih zrncih (sindrom Hermansky-Pudlak (17,18), sindrom Che di ak-Higashi (17,(19)(20)(21), in Grisellijev sindrom (17)), motnje skladiščenja substanc v zrncih alfa (sindrom ARC (angl. arthrogryposis, renal tubular acidosis, cholestasis) (17,22)) in motnje izločanja substanc iz zrnc trombocitov.…”