Chediak-Higashi Syndrome

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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]

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]

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  • Impaired vision
  • Photophobia
  • Albinism of the OCA2 type, giving a lighter complexion than unaffected family members[6]
  • 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]

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]

  • 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.
  • 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.

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]

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]

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

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]

Further reading & references

  1. Sondheimer N; Chediak-Higashi syndrome; Medline Plus
  2. Chediak-Higashi Syndrome; CHS, Online Mendelian Inheritance in Man (OMIM)
  3. Kaplan J, De Domenico I, Ward DM; Chediak-Higashi syndrome. Curr Opin Hematol. 2008 Jan;15(1):22-9.
  4. Nowicki R,Sczarmach S; Chediak-Higashi Syndrome; eMedicine, 2009.
  5. Tanaka T; Chediak-Higashi syndrome: abnormal lysosomal enzyme levels in granulocytes of patients and family members. Pediatr Res. 1980 Aug;14(8):901-4.
  6. Oculocutaneous Albinism, Type II; OCA2, Online Mendelian Inheritance in Man (OMIM)
  7. Misra VP, King RH, Harding AE, et al; Peripheral neuropathy in the Chediak-Higashi syndrome. Acta Neuropathol (Berl). 1991;81(3):354-8.
  8. Hermansky F, Pudlak P; Albinism associated with hemorrhagic diathesis and unusual pigmented reticular cells in the bone marrow: report of two cases with histochemical studies; Blood. 1959 Feb;14(2):162-9.
  9. Scheinfield N, Johnson A; Griscelli Syndrome, eMedicine, 2008.
  10. Valente NY, Machado MC, Boggio P, et al; Polarized light microscopy of hair shafts aids in the differential diagnosis of Chediak-Higashi and Griscelli-Prunieras syndromes. Clinics. 2006 Aug;61(4):327-32.
  11. Trottestam H, Beutel K, Meeths M, et al; Treatment of the X-linked lymphoproliferative, Griscelli and Chediak-Higashi syndromes by HLH directed therapy. Pediatr Blood Cancer. 2009 Feb;52(2):268-72.
  12. Aslan Y, Erduran E, Gedik Y, et al; The role of high dose methylprednisolone and splenectomy in the accelerated phase of Chediak-Higashi syndrome. Acta Haematol. 1996;96(2):105-7.
  13. Liang JS, Lu MY, Tsai MJ, et al; Bone marrow transplantation from an HLA-matched unrelated donor for treatment of Chediak-Higashi syndrome. J Formos Med Assoc. 2000 Jun;99(6):499-502.
  14. Diukman R, Tanigawara S, Cowan MJ, et al; Prenatal diagnosis of Chediak-Higashi syndrome. Prenat Diagn. 1992 Nov;12(11):877-85.

Disclaimer: This article is for information only and should not be used for the diagnosis or treatment of medical conditions. EMIS has used all reasonable care in compiling the information but make no warranty as to its accuracy. Consult a doctor or other health care professional for diagnosis and treatment of medical conditions. For details see our conditions.

Original Author:
Dr Laurence Knott
Current Version:
Last Checked:
15/10/2009
Document ID:
1933 (v21)
© EMIS