Chediak-Higashi syndrome

Chediak–Higashi syndrome (CHS) is a very rare inherited disorder that occurs predominantly in certain Jewish populations. However, the disease is not exclusive to humans and has also been described in cattle, white tigers, blue Persian cats, mice, minks, foxes, and killer whales. The gene mutation causes abnormal lysosomal function. Lysosomes are intracellular vesicles that contain various active compounds; when needed, the contents of these vesicles can be released into the surrounding cellular environment to perform their function.

In many white blood cells, lysosomes contain defensive substances used to destroy bacteria. Disruption of the responsible gene leads to impaired lysosomal degranulation, which subsequently results in a reduced ability of the immune system to fight infections. Many individuals with Chediak–Higashi syndrome die from these infections before reaching adulthood.

Chediak–Higashi syndrome manifests with oculocutaneous albinism (reduced pigmentation); silvery‑blond hair is characteristic. Other typical features include hepatosplenomegaly, lymph node hypertrophy, and recurrent purulent (bacterial) infections of the skin and respiratory tract, which are more severe than in otherwise healthy individuals due to impaired immune function.

Diagnosis

In the peripheral blood smear, abnormalities of leukocyte and lymphocyte granulation are evident (giant granules), as well as plasma inclusions in myeloid cells in the bone marrow. In prenatal diagnosis, the disease may be detected by fetal blood analysis or by biopsy of hair shafts or skin.

The syndrome is inherited in an autosomal recessive manner. The CHS gene is located on the long arm of chromosome 1, at locus q42.1–q42.2. The symptoms result from functional defects of polymorphonuclear leukocytes, which contain characteristic lysosomal vacuoles, and from a deficiency of natural killer (NK) lymphocytes. Research using animal models (mice) led to the identification of a mutation in the gene encoding the LYST protein, whose exact function is still unknown. Chediak–Higashi syndrome is often associated with aggressive periodontitis.

In some cases, the nervous system may also be affected, with possible presence of polyneuropathy, intellectual disability, and epilepsy.

Microscopic examination of white blood cells reveals giant granules, which represent lysosomes that are unable to release their contents. Definitive confirmation of the disease is provided by genetic testing, which detects the presence of the pathogenic mutated gene.

Treatment

Prevention is not known. The syndrome is essentially incurable, although bone marrow transplantation may be performed. The patient’s immune system must be supported, and bacterial infections must be treated aggressively with antibiotics. Despite maximal supportive care, the prognosis remains poor.

• znížená imunita
• časté infekcie
• znížená pigmentácia kože
• striebristo-blond vlasy
• opakujúce sa hnisavé (bakteriálne) infekcie kože a dýchacích ciest
• niekedy postihnutý nervový systém (možnosť prítomnosti polyneuropatie, mentálnej retardácie a epilepsie)