Chediak Higashi Syndrome – Too little, too late?

Abstract

Introduction: Chediak-Higashi syndrome (CHS) is a rare multi-system disorder resulting from mutations in the
Lysosomal Trafficking Regulator Protein (LYST) gene. The resultant dysfunctional vesicular transport causes
severely disturbed cellular functions such as phagocytosis and lysosomal trafficking. Clinically, affected patients
present with recurrent pyogenic infections, partial albinism and peripheral neuropathies. Disease onset is usually
in the first year of life however, late presentations have been reported. Presence of giant neutrophilic granules in
blood smears provide the first clues to diagnosis. Bone marrow transplant improves the immune deficiency. In
resource deprived countries, antibiotic prophylaxis and genetic counselling remains the only option.
Materials and Methods: We report 8 cases diagnosed with CHS between 2008 and 2016 in two tertiary care
hospitals of Peshawar. Complete history and physical examination was performed. In addition, microscopic
examination of Giemsa stained peripheral blood and bone marrow smears was performed. Myeloperoxidase
staining was performed on blood and bone marrow smears.
Results: The mean age of patients at diagnosis was 36 months (range 3 months – 10 years). Main presenting
features were a history of recurrent chest and skin abscesses. All patients had variable degrees of oculocutaneous
albinism and silvery grey hair. Six patients had one or more siblings with similar symptoms or death during
infancy or early childhood. All patients fulfilled the criteria for ‘accelerated phase’ of CHS at diagnosis.
Cytopenias in peripheral blood and hemophagocytosis was invariably present in all patients. Myeloperoxidase
staining of the blood and bone marrow smears showed large peroxidase positive granules in mainly myeloid
cells. Supportive therapy such as prophylactic antibiotics and high dose vitamin C were prescribed and patients
were discharged after the acute episodes. No follow-up was performed.
Conclusion: CHS patients were diagnosed based on clinical presentation and peripheral blood and bone
marrow findings of large myeloperoxidase positive granules in myeloid cells. Most of these patients had been
admitted in hospitals before but were not diagnosed on first admission. The majority of cases presented in
accelerated phase, were discharged without family testing, genetic counselling or bone marrow transplant. In
conclusion, a high-degree of suspicion is necessary for the diagnosis of rare diseases such as CHS. Furthermore, a
pro-active concerted approach by the hematologists and pediatricians is of paramount importance to offer the
available treatment options and genetic counselling.