Chediak-Higashi Syndrome

Authored by Dr Laurence Knott, 15 Oct 2009

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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]

  • 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 and 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 Jan15(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 Aug14(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). 199181(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

  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 Aug61(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 Feb52(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. 199696(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 Jun99(6):499-502.

  14. Diukman R, Tanigawara S, Cowan MJ, et al; Prenatal diagnosis of Chediak-Higashi syndrome. Prenat Diagn. 1992 Nov12(11):877-85.

Interested in hearing peoples symptoms and experiances with this. I had pvd of the left eye and sure enough 6 months later,right eye. Having problems dealing with it. When both eyes are affected,hard...

lee12629
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