Chediak-Higashi syndrome is inherited as an autosomal recessive disease.¹ It was described over 50 years ago. Clinical reports have identified mutations throughout the CHS1/LYST lysosomal trafficking gene.² The nature of the mutation can be a predictor of the severity of the disease.³ There are a number of animal models including mouse, cat, cattle, mink and killer whale.²

Epidemiology

The condition is rare. The literature tends to be isolated case studies or just a few cases.⁴ Family history of the disease is a risk factor but it is uncommon to find a positive history in patients with this condition.⁵

Presentation^1,4

• Impaired vision
• Photophobia
• Albinism of the OCA2 type, giving a lighter complexion than unaffected family members⁶
• 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)⁷

Differential diagnosis

Initially the condition may present as one of the varieties of albinism but the recurrent infections should make one suspect the diagnosis. The Hermansky-Pudlak syndrome and Griscelli's syndrome are similar but distinct conditions.^8,9

Investigations^1,4

• Blood smear shows giant granules in the neutrophils that stain for peroxidases.
• Bone marrow smears show giant inclusion bodies in leukocyte precursor cells.⁴
• Giant granules are also found in cells from biopsy of skin, muscle and nervous system.
• Platelet or leukocyte 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's syndrome.¹⁰
• Fluorescence cytometric analysis of cellular granularity and surface molecules offer useful diagnostic information.⁴
• EEG may be abnormal.
• Brain MRI or CT scan may show small brain due to atrophy.
• Oral radiographs may reveal extensive loss of alveolar bone, often resulting in tooth exfoliation.⁴.
• 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.

Associated diseases

• Infection is a constant problem.⁴
• For a better understanding of the visual defects and the problems related to the OCA2, see the separate record on Albinism.

Management⁴

Drug

• Allogenic bone marrow transplantation (BMT) from an HLA-matched sibling is the treatment of choice but does not prevent the neurological disorders.
• If no related donor is available, an unrelated donor or a placental blood graft may be used.
• Haemopoietic stem cell transplant proved an effective treatment in one study.¹¹
• Antiviral drugs like aciclovir, high-dose intravenous gamma globulin; and microtubulytic drugs, such as vincristine, vinblastine and colchicine, are effective in the management of the accelerated phase. Cyclophosphamide and prednisolone have been tried but without much benefit. High-dose methylprednisolone and splenectomy have produced temporary respite.^1,12
• Frequent infections are treated with antibiotics.

Non-drug

• Abscesses are surgically drained when appropriate.¹
• BMT appears to have been successful in several patients.¹³

Complications

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.^2,4

Prognosis

Without BMT, death before the age of 10 is common.⁴ The terminal phase of the illness is not treatable.^2,4

Prevention

Genetic counselling is recommended for prospective parents with a family history of Chediak-Higashi syndrome.¹⁴ Examination of hair from fetal scalp biopsy specimens and of leukocytes from fetal blood samples can be used for prenatal diagnosis.⁴