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 infections, albinism, 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.

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.

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.

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.

References:

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