Pathogenesis of Chediak-Higashi syndrome

Chediak-Higashi syndrome is inherited autosomal recessive, and it is based on a violation of intracellular protein transport. In 1996, the genetic nature of the Chediak-Higashi syndrome, which was associated with mutations in the LYST / CHS1 gene, was deciphered; it is localized on the long arm of chromosome 1 (lq42-43). The product of this gene is involved in the biogenesis of lysosomes, melanosomes, and secretory granules of cytotoxic cells.

The mutation in the CHS gene leads to a disruption in the formation of intracellular (raun in various cells.) The leiosomes of leukocytes and fibroblasts, dense platelets, azurophilic neutrophil granules, melanocytes melanocytes at CHS are usually much larger in size and morphologically altered, indicating a single pathway for the synthesis of organelles responsible for the storage of synthesized substances.In the early stages of maturation of neutrophils, the normal azurophilic granules merge to the size of megatrans, whereas in later periods (for example, the herd and myelocytes) can form granules of normal size. Mature neutrophils contain both populations. This phenomenon is also observed in monocytes.

Violation of melanin production by melanosomes leads to the development of albinism. In melanocytes, autophagocytosis with melanosomes is observed.

Approximately 80% of patients with Chediak-Higashi syndrome develop a so-called accelerating phase, which is a non-malignant lymphoma-like infiltration of various organs, the cause of which is most often the Epstein-Barr virus infection. Clinically noted anemia, episodic hemorrhages, severe, often fatal, infections. In the infectious process, which is usually caused by Staphylococcus aureus, Streptococcus pyogenes and Pneumococcus sp, "the skin, the respiratory tract, the lungs are most often involved. The phase of acceleration resembles that in other diseases accompanied by lymphocyte / macrophage activation syndrome, in particular, with GLH and Griselli syndrome.

As a rule, the acceleration phase and / or severe infection lead to the death of patients at an early age, but in the literature there are descriptions of adult patients. In such patients, the progressive symptom of the disease was progressive neurological dysfunction, most often in the form of peripheral neuropathy, the development mechanism of which remains unclear until the end. Axonal and demyelinating types of peripheral neuropathy in patients with Chediak-Higashi syndrome are also described.

[1], [2], [3], [4], [5]