Chediak-Higashi Syndrome Workup

Updated: Aug 08, 2019
  • Author: Roman J Nowicki, MD, PhD; Chief Editor: Dirk M Elston, MD  more...
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Laboratory Studies

Diagnosis of Chédiak-Higashi syndrome (CHS) is made by recognition of the characteristic giant granules in neutrophils, eosinophils, and granulocytes by using light microscopy of a routine blood smear. Laboratory findings include neutropenia and hypergammaglobulinemia.

Bone marrow smears reveal giant inclusion bodies in leukocyte precursor cells. The granules are peroxidase positive and contain lysosomal enzymes, suggesting that they are giant lysosomes, or in the case of melanocytes, that they are giant melanosomes. The diagnostic hallmark is the occurrence of giant inclusion bodies in the peripheral leukocytes and their bone marrow precursors. [20]

In addition to the characteristic leukocytic dysfunctions, fluorescence cytometric analysis of cellular granularity and surface molecules offer useful diagnostic information.

Microscopic examination of the hair can also reveal clumped melanin granules, larger than those seen in normal hairs, and examination of the skin shows giant melanosomes both in keratinocytes and melanocytes, which can be us.

Definite diagnosis is based on the molecular genetic testing of CHS1. [14]

Molecular testing approaches can include the following:

  • Sequence analysis of LYST first followed by deletion/duplication analysis if only one or no mutation is found
  • Use of a multigene panel that includes LYST and other genes of interest used as a laboratory test for the differential diagnosis with other partial albinism disorders

Imaging Studies

Oral radiographs reveal extensive loss of alveolar bone, leading to tooth exfoliation in most cases. CT scans and MRIs demonstrate diffuse brain and spinal cord atrophy.


Other Tests

Light and electron microscopic examinations of biopsy specimens of periodontal tissues reveal massive bacterial invasion of epithelial tissue, epithelial cells, and connective tissue.

Ultrastructural observations of periodontal polymorphonuclear leukocytes reveal defective granulation, with abnormal granules not discharging their lysosomal content against the engulfed bacteria. Viable dividing bacteria are found in the cytoplasm.

Prenatal diagnosis can be made by examination of hair from fetal scalp biopsy specimens and of leukocytes from fetal blood samples.


Histologic Findings

A skin biopsy specimen usually appears entirely normal but may show melanin macroglobules and perhaps sparse dermal melanin. Ultrastructural examination reveals large abnormal type stage IV melanosomes that are transferred to keratinocytes with difficulty and are degraded rapidly.