Chediak higashi syndrome E70.3

Rare, autosomal recessive variant of oculocutaneous albinoidism with leukocytic immunodeficiency, consecutive susceptibility to infection, hepatosplenomegaly, generalized lymph node enlargement, and impaired melanogenesis (the syndrome is also listed under"tumor-associated genodermatoses").

This is caused by autosomal recessive inherited defects of the so-called CHS1 gene (Chediak-Higashi gene 1 = LYST gene/lysomal trafficking regulator gene; gene locus: 1q42.1-q42.2). The LYST gene encodes a protein that regulates intracellular protein trafficking in endosomes and may be involved in pigmentation. It regulates the cleavage of intracellular vesicles such as lysosomes (Holland P et al. 2014). In cytotoxic T cells and natural killer (NK) cells, it plays a role in regulating the size, number and exocytosis of lytic granules. The mutation in this gene leads to a disruption of lysosome biogenesis with lysosomal giant granules. In melanocytes, this gene defect leads to giant melanosomes with defective localization of melanosome-specific proteins(tyrosinase/TYRP1) in large vesicular structures of the cytoplasm. As a result of the impaired function of the immune cells, a primary immunodeficiency syndrome also occurs (Bowman SL et al. 2019).

Signs of immunodeficiency such as pyoderma or respiratory tract infections are already evident in the first months of life.

Skin symptoms can be the first symptom of this systemic disease.

Furthermore, there are neurological currents with peripheral neuropathies, balance disorders and cognitive impairment.

Partial oculocutaneous albinism is regularly found.

Less frequently, lymphohistiocytosis develops.

Blood count: Characteristic granulation of the leukocytes (giant lysosomes) in the blood smear; neutropenia, among others

Bone marrow transplantation is the only possible curative therapy for the leukocyte defect. Use of high doses of aciclovir, gamma globulin, vincristine, s.a. cytostatics, prednisolone in lymphoproliferative phases is described. Splenectomy may be helpful if therapy is resistant. High doses of ascorbic acid (1 g/day) prophylactically against susceptibility to infections.

Otherwise: photoprotective agents (e.g. Anthelios, Eucerin Sun, regular eye monitoring and sunglasses, avoidance and remediation of infections.

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