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
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
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.
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 (creatinine, blood urea nitrogen) should be
assessed if the patient is taking high doses of vitamin C. Patients may be
on long-term steroid therapy.
Strict precautions to prevent iatrogenic
infections in these immunologically compromised patients should be taken.
Regional anesthesia, particularly central neuraxial blockade, is relatively
contraindicated in ...