Chédiak–Higashi syndrome

Chédiak–Higashi syndrome
ICD-10	E70.3 (E70.340 ILDS)
ICD-9	288.2
DiseasesDB	2351
MedlinePlus	001312
eMedicine	derm 704
MeSH ID	D002609

Chédiak–Higashi syndrome (CHS) is an uncommon autosomal recessive disorder characterized by a mutation in the lysosomal trafficking regulator protein, resulting in diminished phagocytosis. This reduction contributes to several clinical manifestations including recurring pyogenic infections, partial albinism, and peripheral neuropathy.

Epidemiology

The syndrome has been observed not only in humans but also in cattle, white tigers, blue Persian cats, Australian blue rats, mice, mink, foxes, and even in the singular known captive albino orca.

Signs and Symptoms

Individuals diagnosed with CHS typically exhibit light skin and silvery hair due to partial albinism, and they often suffer from solar sensitivity and photophobia. Notable manifestations include:

• Frequent infections involving the mucous membranes, skin, and respiratory tract.
• Infections predominantly caused by both Gram-positive and gram-negative bacteria, and fungi. Notably, Staphylococcus aureus is a common causative agent.
• Neuropathy, especially prominent in teenage years.
• Serious, sometimes fatal infections.

A significant number of children with CHS progress to what's known as the accelerated phase or lymphoma-like-syndrome. This phase is typically instigated by a viral infection, often attributed to the Epstein-Barr virus (EBV). During this phase, malfunctioning white blood cells proliferate uncontrollably, affecting various organs. Symptoms include fever, abnormal bleeding episodes, rampant infections, and organ failure.

Causes

The primary cause of Chédiak–Higashi Syndrome is mutations in the CHS1 gene (or LYST). This gene facilitates the creation of a protein known as the lysosomal trafficking regulator, vital for the transportation of materials into lysosomes. Lysosomes function as cellular recycling hubs, breaking down toxic substances, digesting invasive bacteria, and recycling cell components. The precise function of the lysosomal trafficking regulator protein in this context remains under research.

Pathophysiology

CHS is characterized by defective bacteriolysis due to the failed formation of phagolysosomes. This intracellular trafficking disorder results in defective lysosome degranulation with phagosomes, preventing the destruction of phagocytosed bacteria by the lysosome's enzymes.

Moreover, the disease hinders the secretion of lytic secretory granules by cytotoxic T cells. Characteristically, the syndrome displays large lysosomal vesicles in phagocytes (neutrophils), contributing to a compromised bactericidal function and hence heightened susceptibility to infections.

Diagnosis

Definitive diagnosis of CHS is achieved by inspecting bone marrow smears, which typically reveal "giant inclusion bodies" in leukocyte precursor cells. Prenatal diagnoses are possible either by analyzing a hair sample from a fetal scalp biopsy or by evaluating leukocytes from a fetal blood sample.

When examined under light microscopy, hairs from affected individuals show uniformly spaced, larger-than-usual melanin granules. Under polarized light microscopy, these hairs display a distinctively bright and polychromatic refringence pattern.

Clinical findings

Key manifestations of CHS encompass neutropenia, oculocutaneous albinism, and an enhanced susceptibility to infections, primarily from Staphylococcus aureus and Streptococci. Additionally, CHS is associated with periodontal disease of the deciduous dentition. The syndrome also presents with melanocyte abnormalities (albinism), nerve defects, and bleeding disorders.

Treatment

While no specific treatment exists for Chédiak–Higashi syndrome, bone marrow transplants have demonstrated efficacy in several patients. Infections are typically addressed with antibiotics, and surgical drainage is employed for abscesses as required. Antiviral agents, like acyclovir, are administered during the disease's terminal phase. Other treatments that have been explored include cyclophosphamide, prednisone, and Vitamin C therapy – the latter occasionally showing improved immune functionality and clotting.

Eponym

Chédiak–Higashi syndrome derives its name from Cuban physician and serologist Alejandro Moisés Chédiak and Japanese pediatrician Otokata Higashi. In various literature, the syndrome is often spelled without the accent: Chediak–Higashi syndrome.

See also

• Griscelli syndrome (also termed "Chédiak–Higashi-like syndrome")

Chédiak–Higashi syndrome Resources
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