Chediak-Higashi Syndrome

Chediak-Higashi Syndrome

Chediak-Higashi syndrome (CHS) is a very rare autosomal recessive primary immunodeficiency disorder that arises from a mutation of a lysosomal trafficking regulator protein, which leads to a decrease in phagocytosis and impaired lysis of phagocytized bacteria, resulting in recurrent bacterial respiratory and other infectionsalbinism, a bleeding tendency, and often progressive neurological disease. Chediak-Higashi syndrome was described over 50 years ago.

Initially, the condition may present as one of the varieties of albinism but the recurrent infections should make one suspect the diagnosis.

Family history of the disease is a risk factor but it is uncommon to find a positive history in patients with this condition.

Chediak-Higashi Syndrome blood smear

Diagnosis of Chediak-Higashi syndrome (CHS) is made by Genetic testing and recognising the characteristic giant granules in neutrophils, eosinophils, and other cells (e.g. lymphocytes, melanocytes, neural Schwann cells).

Bone marrow smears reveal giant inclusion bodies in leukocyte precursor cells.

Laboratory findings include neutropenia and hypergammaglobulinemia.

Infants born with Chediak-Higashi syndrome (CHS) have nonpigmented skin (similar to albinos but in patchy distribution), blonde hair, and blue eyes.

Chédiak-Higashi's Syndrome

Signs and symptoms include the following:

  • Lymphadenopathy
  • Enlarged liver and spleen
  • Jaundice
  • Albinism, impaired vision, photophobia
  • Aphthae (a small, shallow, painful ulceration that usually affects the oral mucosa, but not underlying bone. Aphthae occasionally may affect other body tissues, including those of the GI tract and the external genitals. They do not appear to be infectious, contagious, or sexually transmitted)
  • Gingivitis
  • Hyperhidrosis (a condition characterized by excessive sweating)
  • Miliaria (skin disease marked by small and itchy rashes)
  • Severe and extensive pyoderma
  • Recurrent sinopulmonary infections
  • Fever unrelated to recognizable infection
  • Epilepsy
  • Mental retardation
  • Ataxia causing incoordination and a typical ataxic gait
  • Tremor
  • Peripheral neuropathy causes motor and sensory changes and weakness (if the patient survives into adulthood)

Case Report:

A 2-year-old girl presented with recurrent infections, hepatosplenomegaly, and photophobia. On examination, she had blond hair with a metallic sheen. The blood smear showed giant lysosomes in the white blood cells and a diagnosis of Chediak-Higashi syndrome was made. CHS is a rare autosomal recessive disease (gene CHS1/LYST at 1q42.1-2). Giant cytoplasmic granules are pathognomonic. Death often occurs before the age of 7 years because of the so-called accelerated phase, with hepatosplenomegaly, lymphadenopathy, and pancytopenia or severe recurrent bacterial infections. The laboratory diagnosis was supported by partial oculocutaneous albinism and typical microscopic granules in hair shafts. A new mutation was identified and the patient was found to be homozygous for a sequence change in the LYST gene.

giant cytoplasmic granules

Blood film showing pathognomonic giant cytoplasmic granules in neutrophils and eosinophils (A), neutrophils (B), and lymphocytes (C, D). 

Treatment includes supportive care using antibiotics, interferon-gamma and sometimes corticosteroids and Bone marrow transplantation.

Prophylactic antibiotics can help prevent infections, and interferon-gamma can help restore some immune system function. Pulse doses of corticosteroids and splenectomy sometimes induce transient remission. However, unless bone marrow transplantation is done, most patients die of infections by the age of 7 years.

Allogeneic transplantation from an HLA-matched sibling or from an unrelated donor or cord blood transplantation is the treatment of choice to correct the immunologic and hematologic manifestations of early-onset Chédiak-Higashi syndrome (CHS).

Summary: Chediak-Higashi Syndrome is a rare genetic disorder affecting multiple body systems. The disorder is caused by mutations in the LYST gene and is characterized by partial albinism, immunodeficiency, and neurological abnormalities. Diagnosis is based on clinical features and confirmed by genetic testing. Treatment is symptomatic and supportive, with hematopoietic stem cell transplantation being a potentially curative option.


Kaplan J, De Domenico I, Ward DM. Chediak-Higashi syndrome. Curr Opin Hematol. 2008 Jan. 15(1):22-9.

Roman J Nowicki, MD. Chediak-Higashi Syndrome: Practice Essentials, Background, Pathophysiology

Delcourt-Debruyne EM, Boutigny HR, Hildebrand HF. Features of severe periodontal disease in a teenager with Chédiak-Higashi syndrome. J Periodontol. 2000 May. 71(5):816-24.

Liang JS, Lu MY, Tsai MJ, Lin DT, Lin KH. Bone marrow transplantation from an HLA-matched unrelated donor for treatment of Chediak-Higashi syndrome. J Formos Med Assoc. 2000 Jun. 99(6):499-502.

Nowicki R, Sczarmach S. Chediak-Higashi Syndrome eMedicine, 2009.

Tanaka T; Chediak-Higashi syndrome: abnormal lysosomal enzyme levels in granulocytes of patients and family members. Pediatr Res. 1980 Aug 14(8):901-4.

Misra VP, King RH, Harding AE, et al. Peripheral neuropathy in the Chediak-Higashi syndrome. Acta Neuropathol (Berl). 1991 81(3):354-8.

Introne WJ, Westbroek W, Golas GA, et al. Chediak-Higashi syndrome: advances in the understanding of lysosomal defects. Expert Rev Clin Immunol. 2015;11(8):1097-1111.

Kaplan J, De Domenico I, Ward DM. Chediak-Higashi syndrome. Curr Opin Hematol. 2008;15(1):22-29.

Menasche G, Feldmann J, Houdusse A, et al. Biochemical and functional characterization of Rab27a mutations occurring in Griscelli syndrome patients. Blood. 2003;101(7):2736-2742.

Antunes Henedina, Pereira Ângela, Cunha Isabel. Chediak-Higashi syndrome: pathognomonic feature – The Lancet.

Chediak-Higashi Syndrome
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Chediak-Higashi Syndrome
Chediak-Higashi syndrome is a rare autosomal recessive lysosomal disorder characterized by frequent infections, albinism, bleeding, and neurologic findings.
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  • Talha Vaqar


    I am writing a text for board review. I find the images used in this resource wonder and I would like to use some of them. I see that it say CC BY-SA 2.0 at the bottom which tells me I could use it even commercially. I write just to confirm.

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