A frequently fatal disease of childhood characterized by the association of immune deficiency, partial oculocutaneous albinism, easy bruisability, bleeding, and recurrent infections.
Chediak-Steinbrinck-Higashi Syndrome; Beguez Cesar Syndrome; Oculocutaneous Albinism Type VIB.
First described by the Cuban pediatrician A. Beguez Cesar in 1943. The German physician W. Steinbrinck, the Cuban physician A.M. Chédiak, and the Japanese pediatrician O. Higashi reported their findings in 1948, 1952, and 1953, respectively.
Approximately 200 cases have been described in the literature. Most affected patients are of Spanish or South American descent.
Autosomal recessive. Caused by mutations in the lysosomal trafficking regular gene CHS1, which is located on 1q42.1-q42.2.
The defective melanosome transfer is a secondary phenomenon of a primary defect in the lysosome trafficking regulator (LYST) protein, a membrane-associated molecule that is important in protein docking and fusion and membrane stability. This is an imperfect oculocutaneous albinism with giant melanosomes. Giant peroxidase-filled lysosomal granules exist in leukocytes, and giant peroxidase-containing granules are present in Schwann cells.
In addition to the features of albinism, photophobia, hypopigmentation, and loss of binocular vision, patients with Chediak-Higashi Syndrome show marked susceptibility to infections. Death often occurs in the first decade of life as a result of infections, bleeding, and the accelerated lymphoma-like phase. However, survival into the second and third decade of life has been reported.
Staphylococcal and streptococcal infections are the most common reason for medical presentation. Immunosuppression can result in potentially life-threatening infections. Anemia, thrombocytopenia, and neutrophilia may develop. Other features can affect neurologic function with peripheral neuropathy and occasionally seizures. Most patients who survive their childhood frequently develop an accelerated phase of the disease characterized by lymphohistiocytic proliferation and hemophagocytic syndrome. In this accelerated phase, patients exhibit mediastinal and hilar lymphadenopathy, jaundice, hepatosplenomegaly, gingivitis, and a pseudomembranous sloughing of the buccal mucosa. Often this seems to be precipitated by viral infections, particularly the Epstein-Barr virus. Platelet function may be impaired before the accelerated phase of the disease because of functional platelet storage defects. Treatment with high doses of ascorbic acid has been beneficial in these patients. However, such high doses of vitamin C have been associated with renal impairment and calculi. Treatment with bone marrow transplantation has been performed.
Precautions before anesthesia
Patients may present for surgical treatment of abscesses. They may be severely septic. A thorough history and examination should be performed to confirm hepatosplenomegaly, which is suggestive of serious end-stage disease. A complete blood count reveals cellular abnormalities. Platelet function tests and bleeding time should be obtained, particularly when major surgery and/or central neuraxial blockade is contemplated. Kidney function ...