Chediak-Higashi Syndrome

Excerpt

Clinical characteristics: Chediak-Higashi syndrome (CHS) is characterized by partial oculocutaneous albinism, immunodeficiency, and a mild bleeding tendency. Approximately 85% of affected individuals develop the accelerated phase, or hemophagocytic lymphohistiocytosis, a life-threatening, hyperinflammatory condition. All affected individuals including adolescents and adults with atypical CHS and children with classic CHS who have successfully undergone allogenic hematopoietic stem cell transplantation (HSCT) develop neurologic findings during early adulthood.

Diagnosis/testing: The diagnosis of CHS is established in a proband with giant inclusions within leukocytes on peripheral blood smear and/or by the identification of biallelic pathogenic variants in LYST on molecular genetic testing.

Management: Treatment of manifestations: Initial chemoimmunotherapy followed by transition to continuation therapy for the accelerated phase; allogenic HSCT as soon as possible to cure hematologic and immunologic defects; L-dopa may be considered for those with parkinsonism; home modifications and intensive rehabilitation for those with ataxia and other neurologic complications; corrective lenses to improve visual acuity; sunglasses to protect sensitive eyes from UV light; sunscreen to prevent sun damage and skin cancer.

Prevention of secondary complications: Prompt aggressive use of antibiotics and antiviral agents for bacterial and viral illnesses; routine inactivated immunizations; intravenous DDAVP prior to invasive procedures to help control bleeding. Platelet transfusions as needed for serious bleeding.

Surveillance: Routine monitoring for chimerism, as 20%-30% donor chimerism is likely enough to protect against reactivation. Yearly ophthalmologic, neurologic, and dermatologic examinations. For atypical or adolescent- or adult-onset CHS: annual abdominal ultrasound examination for hepatosplenomegaly; complete blood count for cytopenias; measurement of serum ferritin concentration and soluble interleukin-2 receptor; and monitoring for liver dysfunction.

Agents/circumstances to avoid: Nonsteroidal anti-inflammatory drugs, which can exacerbate the bleeding tendency; live vaccines.

Genetic counseling: CHS is inherited in an autosomal recessive manner. When both parents are heterozygous, each sib of an affected individual has a 25% chance of being affected, a 50% chance of being an asymptomatic carrier, and a 25% chance of being unaffected and not a carrier. Prenatal testing of CHS is possible if the pathogenic variants have been identified in the family.