LYST gene
OMIM#214500 https://omim.org/entry/214500
1. The disease
Chediak-Higashi syndrome (CHS) is a rare severe genetic disorder generally characterized by partial oculocutaneous albinism, severe immunodeficiency, mild bleeding, neurological dysfunction and lymphoproliferative disorder. A classic, early-onset form and an attenuated, later-onset form (Atypical CHS) have been described.
2. The symptoms
Infants are usually initially asymptomatic at birth except for the loss of pigmentation of hair, skin and eyes. Lack of early signs or symptoms does not exclude the diagnosis.
- Patients with CHS mostly have partial OCA involving the hair, skin, and eyes. Reduced iris pigmentation may be associated with nystagmus, and visual acuity may be impaired.
- Infections which are predominantly bacterial, but also of viral or fungal origin, begin to occur in infancy and may be severe, affecting primarily the skin and upper respiratory tract. Periodontitis has often been reported.
- Manifestations of increased bleeding tendency are generally mild and include epistaxis, gum bleeding and easy bruising.
- Cognitive deficits are often noted in childhood. Most patients develop neurological features by early adulthood as the disease progresses including ataxia, tremor, absent deep-tendon reflexes, and peripheral neuropathy. Some patients have parkinsonian features with bradykinesia and rigidity.
- About 85% of CHS patients develop the accelerated phase, a lymphoproliferative disorder, which involves fever, anemia, neutropenia, and occasionally thrombocytopenia, as well as lymphadenopathy and hepatosplenomegaly.
3. Actions to take in case of early diagnosis
- Infants with a positive genetic test (having 2 mutations or 2 copies of a single mutations in the LYST gene) should continue breastfeeding
- Infants with a positive genetic test should have a blood smear for the identification of giant inclusions within leukocytes.
- CHS is a lifelong condition that requires lifetime management and regular follow-up with an immunology specialist and a multidisciplinary approach to care, including dermatology, pediatrics and genetics.
- Infections should be treated promptly with antibiotics or antivirals and exposure to infectious agents avoided.
- The haematological and immunological manifestations can be treated by allogeneic hematopoietic stem cell transplantation (HSCT) upon diagnosis. HSCT is more successful when performed before the accelerated phase, but does not alter progression of neurological dysfunction.
- Management of the acceleration phase involves combination therapy with etoposide, dexamethasone, and cyclosporine.
- Desmopressin can be used for bleeding prophylaxis.
- Standard therapeutic measures should be adopted to improve visual acuity and to manage neurological manifestations. Patients should use sunscreen and wear protective UV sunglasses.
- Genetic counselling is highly recommended for family planning and evaluation of at-risk family members.
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