The Chediak Higashi syndrome - Primary Immunodeficiency Disease

The Chediak-Higashi syndrome

Chediak-Higashi syndrome (CHS) is a rare autosomal recessive disorder first described in 1943. It is sometimes classified as a phagocytic defect.

However, even though phagocytic cells, such as neutrophils and monocytes, are defective, Natural Killer (NK) cells, which form the first line of defence against viruses, are also abnormal. The syndrome arises from a mutated form of the CHS1 gene located on chromosome 1. The gene product is involved in the intracellular transport of proteins and the synthesis of storage granules in certain cells. The mutation results in neutrophils with abnormally large or ‘giant’ lysosomes and platelets with abnormal dense bodies. In addition, melanocytes, the pigment-producing cells of the skin, contain larger than normal melanosomes; the pigment storing organelles.

Chediak-Higashi syndrome presents as an immune deficiency that leads to recurrent bacterial infections, most commonly with Staphylococcus aureus,Streptococcus pyogenes, and Pneumococcus spp and viral infections, suchas with Epstein-Barr virus, that frequently result in tumors of the lymph nodes (lymphomas). Leukocyte counts reveal neutropenia and abnormal neutrophils that do not respond to chemotactic molecules, for example activated complement proteins, and which fail to kill ingested bacteria. Infants suffer recurrent skin infections, which may result in ulcers and abscesses. The abnormalities of melanocytes means that patients are deficient in skin pigment and have blond hair and translucent blue eyes. Infants also bruise very easily, due to defective platelets. In addition, they suffer progressive neurological dysfunction, with abnormal gait, mental retardation and peripheral neuropathy. If the child survives beyond the first decade this may lead to Parkinsonism and/or dementia. Morbidity and mortality are high in CHS, with infants frequently dying before the age of 10 years, usually from overwhelming pyogenic infections attributable to poor neutrophil function.

The recommended treatment for children with CHS is a bone marrow transplant to correct the immune deficit. However, success has been variable and this treatment has no effect on the lack of pigmentation since melanocytes do not arise from bone marrow. Antibiotics are given to treat bacterial infections and antiviral drugs, such as acyclovir or interferon @, to limit infection with the Epstein-Barr virus. Patients with lymphoma are given anticancer drugs, such as vincristine.