Chediak-Higashi syndrome is a rare autosomal recessive disorder that causes infections and oculocutaneous albinism that can progress to neurologic abnormalities and coagulation defects. The underlying defect of Chediak-Higashi syndrome is an abnormality of the fusion of vesicles and failure of lysosomal transportation due to a mutation in the CHS1/LYST gene.
Clinical Symptoms
There are a variety of clinical manifestations that occur with this disease. Usually, symptoms present in early childhood when they present with recurrent infections with unknown causes. Infections are frequent and quite severe due to neutrophil dysfunction in the skin, respiratory tract, and mucous membranes. The most common organisms causing infections are Staphylococcus aureus, Streptococcus pyogenes, and Pneumococcus species. There is also hypopigmentation that varies between individuals. This typically affects fair skin and sparse light-blond, gray, or white hair, and pigmentation of the retina is also reduced. Other ocular manifestations include photophobia, decreased visual acuity, nystagmus, and strabismus. Coagulation defects can also occur and this can be seen in patients as easy bruising and abnormal bleeding. Gingivitis, oral ulcerations, and periodontal disease are also common in this disorder due to defective toll-like receptor expression and function. Neurologic dysfunction can also be a common manifestation and can lead to sensory deficits due to peripheral neuropathy, ataxia, tremors, cranial nerve palsies, and seizures. Patients that are in their 20s or 30s are more susceptible to spinocerebellar degeneration, Parkinson's disease-like movement, and dementia.
Diagnosis
There are several diagnostic findings with Chediak-Higashi Syndrome. A common lab finding is neutropenia due to the impairment of the natural immune system to fight off bacteria. Thrombocytopenia is also common and can be seen on a routine CBC. On a CT scan and MRI, there can be diffuse atrophy of the brain and spinal cord. There can also be delayed nerve conduction time on the EMG. Giant granules are seen in Schwann cells and muscle cells and skin melanocyte examination can reveal giant melanosomes. Hair shafts can show small aggregates of clumped pigmentation that are regularly distributed. A peripheral blood smear can show giant azurophilic granules in neutrophils, eosinophils, and other granulocytes. Confirmation of disease is only done with genetic testing for the CHS1/LYST gene.
Treatment and Prognosis
Treatment of Chediak-Higashi Syndrome involves aggressive prophylactic antibiotics for acute bacterial infections and granulocyte colony-stimulating factors to correct neutropenia to prevent future infections. Transplantation of cord blood can be successful if human leukocyte antigen identical donor is used as well. High-dose glucocorticoids and splenectomy have also been used to induce transient remission. Intravenous immune globulin, antivirals such as acyclovir, and chemotherapy can also induce remission. Most patients with Chediak-Higashi Syndrome will die from pyogenic infections or hemorrhage before seven years old if not transplanted with cord blood. Long-term deficits include cerebellar ataxia, difficulty walking, and loss of balance. Clinicians need to identify this disease and differentiate it from other similar diseases such as Griscelli syndrome or Hermansky-Pudlak syndromes to provide effective and quick treatment to patients for remission.
Resources
Boztug, K. (n.d.). UpToDate. UpToDate. https://www.uptodate.com/contents/chediak-higashi-syndrome?search=chediak%20higashi&source=search_result&selectedTitle=1%7E36&usage_type=default&display_rank=1#H9 Assessed and Endorsed by the MedReport Medical Review Board