Clinical aspects and main diagnostic methods of Chediak-Higashi syndrome

Chediak-Higashi syndrome is a disorder caused by a mutation in the LYST gene and characterized by immunodeficiency, oculocutaneous albinism, and neurological dysfunction resulting from changes in neutrophils. Homozygotes die in the first decade of life. The study is a literature review from different sources. We extracted articles published between 2000 and 2018 from SciELO, LILACS, MEDLINE (via PubMed), and Google Scholar databases. Our main objective was to report pathophysiology, clinical presentation, and the most common diagnostic methods. The syndrome affects the hematological and neurological systems, and laboratory diagnosis is first made by the presence of giant granules in leukocytes, mainly neutrophils in peripheral blood and bone marrow. A definitive diagnosis is made by cytochemical reaction (myeloperoxidase) and detection of mutation by molecular methods. (AU)

Inflammatory demyelinating neuropathy heralding accelerated chediak-higashi syndrome.

INTRODUCTION: Chediak-Higashi syndrome (CHS) is a very rare autosomal recessive disorder (gene CHS1/LYST) characterized by partial albinism, recurrent infections, and easy bruising. Survivors develop a constellation of slowly progressive neurological manifestations. METHODS: We describe clinical, laboratory, electrophysiological, and genetic findings of a patient who developed an immune-mediated demyelinating neuropathy as the main clinical feature of CHS. RESULTS: The patient presented with subacute flaccid paraparesis, absent reflexes, and reduced vibration sense. Protein and immunoglobulins (Igs) were elevated in the cerebrospinal fluid. Electrodiagnostic tests indicated an acquired chronic demyelinating polyneuropathy. Intravenous Ig and immunosuppressant treatment resulted in neurological improvement. The patient later developed organomegaly and pancytopenia. Bone-marrow smear revealed giant azurophilic granules pathognomonic for CHS. Two novel mutations in the LYST gene were identified through whole exome sequencing [c.7786C>T and c.9106 + 1G>T]. CONCLUSIONS: This case expands the clinical phenotype of CHS and highlights inflammatory demyelinating neuropathy as a manifestation of the disease. Muscle Nerve 55: 756-760, 2017.

Chediak-Higashi syndrome with parkinsonism.

Chediak-Higashi syndrome (CHS), typically presents with partial albinism and severe hematological abnormalities. About 10% of the patients have a mild adult form associated with various neurological manifestations. We describe the case of a 24-year-old woman with parkinsonism that responded well to antiparkinsonian drugs.

Chédiak-Higashi syndrome: presentation of seven cases

Context: Chédiak-Higashi Syndrome (CHS) is a rare autosomal recessive disease characterized by recurrent infections, giant cytoplasmic granules, and oculocutaneous albinism. Objective: To describe clinical and laboratory findings from CHS patients. Design: Case report. Setting: The patients were admitted into the Allergy and Immunology Unit of the Instituto da Criança, a tertiary public care institution. Cases Report: Seven patients had oculocutaneous albinism, recurrent infections and giant cytoplasmic granules in the leukocyte. One patient had low IgG levels and three showed impaired bactericidal activity of neutrophils. Six patients died of infectious complications during the accelerated phase. Therapy included ascorbic acid and antibiotics. Chemotherapy was used for the accelerated phase in two patients. Bone marrow transplantation (BMT) was proposed for one patient. Discussion: The authors emphasize the need for early diagnosis and therapy of CHS. BMT should be indicated before the accelerated phase of the disease has developed.

Síndrome de Chediak-Higashi: relato de caso e revisäo de literatura / Chediak-Higashi syndrome: case report and literature review

Objetivo: Apresentar o caso de paciente parda portadora de síndrome de Chediak-Higashi (SCH). Método: Além dos dados de história clínica e de exame físico a paciente foi submetida a investigação laboratorial para imunodeficiência. Resultados: As principais manifestações clínicas da paciente eram albinismo parcial óculo-cutâneo e infecções de repetição. Os exames laboratoriais revelaram a presença de inclusões intracitoplasmáticas gigantes em leucócitos do sangue periférico e em células precursoras na medula óssea. A avaliação funcional dos leucócitos do sangue periférico foi normal. Quatro meses após o diagnóstico, a criança desenvolveu a fase linfoproliferativa evoluindo para óbito. Conclusões: São discutidas as principais alterações laboratoriais que caracterizam a SCH, tece-se comentários sobre os possíveis fatores etiológicos, bem como os avanços no seu tratamento.

Chédiak-Higashi syndrome: presentation of seven cases.

CONTEXT: Chédiak-Higashi Syndrome (CHS) is a rare autosomal recessive disease characterized by recurrent infections, giant cytoplasmic granules, and oculocutaneous albinism. OBJECTIVE: To describe clinical and laboratory findings from CHS patients. DESIGN: Case report. SETTING: The patients were admitted into the Allergy and Immunology Unit of the Instituto da Criança, a tertiary public care institution. CASES REPORT: Seven patients had oculocutaneous albinism, recurrent infections and giant cytoplasmic granules in the leukocytes. One patient had low IgG levels and three showed impaired bactericidal activity of neutrophils. Six patients died of infectious complications during the accelerated phase. Therapy included ascorbic acid and antibiotics. Chemotherapy was used for the accelerated phase in two patients. Bone marrow transplantation (BMT) was proposed for one patient. DISCUSSION: The authors emphasize the need for early diagnosis and therapy of CHS. BMT should be indicated before the accelerated phase of the disease has developed.

Delayed phagocytosis and bacterial killing in Chediak-Higashi syndrome neutrophils detected by a fluorochrome assay. Ultrastructural aspects.

The few studies already published about phagocyte functions in Chediak-Higashi syndrome (CHS) has stated that neutrophils present slow rate of bacterial killing but normally ingest microorganisms. In the present study, both phagocytosis and killing of Staphylococcus aureus were verified to be delayed in neutrophils from two patients with CHS when these functions were simultaneously evaluated by a fluorochrome phagocytosis assay. Electron microscopic examination showed morphologic differences among neutrophils from CHS patients and normal neutrophils regarding the cytoplasmic structures and the aspects of the phagolysosomes. It was noteworthy the presence of giant phagolysosomes enclosing bacteria in active proliferation commonly observed in CHS neutrophils after 45 min of phagocytosis, which corresponded with the impaired bactericidal activity of these leukocytes. The present results suggest that phagocytosis may also be defective in CHS, and point out to the sensitivity of the fluorochrome phagocytosis assay and its application in clinical laboratories.

Functions of neutrophils in endemic Chediak-Higashi syndrome.

Endemic Chediak-Higashi Syndrome occurs in a restricted geographic area (Pregonero, State of Táchira, Venezuela). Neutrophils from these patients were unable to digest Candida albicans in vitro, but showed normal or increased metabolic activities. This finding supports the view that the endemic syndrome is bona fide Chediak-Higashi Syndrome.