Chediak-Higashi Syndrome

Chediak-Higashi syndrome is inherited as an autosomal recessive disease.¹ The primary defect is caused by mutation of the lysosomal trafficking gene (LYST).² There are a number of animal models including mouse, cat, cattle, mink and killer whale.²

The condition is rare. The literature tends to be isolated case studies or just a few cases.³
Family history of the disease is a risk factor, but it is uncommon to find a positive history in patients with this condition.⁴

• Impaired vision
• Photophobia
• Albinism of the OCA2 type giving a lighter complexion than unaffected family members⁵
• Silvery sheen to hair which may be fair in colour
• Frequent infections (skin, mucous membranes, respiratory)
• Epilepsy
• Mental retardation
• Enlarged liver and spleen
• Jaundice
• Ataxia causing incoordination and a typical ataxic gait
• Tremor
• Epilepsy
• Peripheral neuropathy causing motor and sensory changes and weakness (if patient survives into adulthood)⁶

Initially the condition it may present as one of the varieties of albinism but the recurrent infections should make one suspect the diagnosis. The Hermansky-Pudlak syndrome is similar but distinct (albinism with life-long bleeding tendency).⁷

• Blood smear shows giant granules in the neutrophils that stain for peroxidases.
• Giant granules are also found in cells from biopsy of skin, muscle and nervous system.
• Platelets or leukocytes levels are abnormally low.
• Genetic testing may show mutations in the CHS1 gene.
• Light or polarised light examination of hair shafts can help to diagnose Chediak-Higashi Syndrome but cannot differentiate it from the appearance seen in Griscelli-Prunieras syndrome (partial albinism with immunodeficiency).⁸
• EEG may be abnormal.
• Brain MRI or CT scan may show small brain due to atrophy.
• EMG or nerve conduction velocity testing may show delayed nerve conduction.
• A red light reflex is present in the eye (this is frequently seen in albinism).
• There are abnormalities of immune function including reduced level of CD4 lymphocytes.

• Infection is a constant problem.³
• For a better understanding of the visual defects and the problems related to the OCA2 see the record on Albinism.

Drug

• There is no specific treatment for Chediak-Higashi syndrome.
• Antiviral drugs like acyclovir have been tried during the terminal phase of the disease. Cyclophosphamide and prednisolone have been tried but without much benefit. High dose methyl prednisolone and splenectomy have produced temporary respite.^1,9
• Frequent infections are treated with antibiotics.

Non-Drug

• Abscesses are surgically drained when appropriate.¹
• Bone marrow transplantation appears to have been successful in several patients.¹⁰

Frequent infections lead to hypersplenism which in turn causes thrombocytopenia and haemorrhage. About 85 to 90% of patients develop an unusual lymphoma. This is called the accelerated phase and is characterised by generalised lymphohistiocytic infiltrates, fever, jaundice, hepato-splenomegaly, lymphadenopathy, pancytopenia and bleeding.^2,3

Death is common before 7 years old. The terminal phase of the illness is not treatable.^2,3 Bone marrow transplantation is a possible cure.¹⁰

Genetic counselling is recommended for prospective parents with a family history of Chediak-Higashi. Intrauterine prenatal diagnosis is possible, but not yet widely available for this disease.¹¹