MYELOPEROXIDASE DEFICIENCY

 

MYELOPEROXIDASE DEFICIENCY

 

DEFINITION:

A disorder of neutrophil function characterized by dysfunctional azurophil granules resulting in mild or no clinical features.

EPIDEMIOLOGY:

  • incidence: ½,000
  • age of onset:
    • ?
  • risk factors:
    • familial - autosomal recessive
      • chrom.#: 17q21.3-q22
      • gene: ?

PATHOGENESIS:

1. Background

  • neutrophils contain two distinct sets of granules: azurophils and specific

    1. Azurophil Granules

    • peroxidase positive
    • form only during myeloblast and promyelocyte differentiation
    • contain unique bactericidal proteins
      • peroxidase, defensins, lysozyme
    • contain unique acid hydrolases and neutral proteinases
      • cathepsins, elastase
    • contain myeloperoxidase (MPO) which is essential for the chlorination and iodination of microbes ingested by neutrophils

2. Genetic Defect

  • genetic defect -> pretranslational defect -> diminished amounts of MPO mRNA -> dysfunctional MPO protein in neutrophils and monocyte azurophilic granules -> partial compromise of bacteri-cidal activity (in vitro) -> in vivo deficiency can be compen-sated for by non-oxidative bactericidal mechanisms -> no or only mild clinical features

CLINICAL FEATURES:

  • majority of patients are asymptomatic
  • recurrent candidal infections in those with:
    • diabetes mellitus
    • other immunosuppressive disorders

INVESTIGATIONS:

1. CBC

  • 2,000-15,000 WBC's (50-70% PMN's)

2. Neutrophil Function

  • chemotaxis - normal
  • superoxide release - increased
  • bacterial killing
    • mildly decreased
    • minor defects in killing of S. aureus
    • impaired killing of C. albicans

3. Cytochemistry (Wright Stain)

  • lack of peroxidase activity
  • normal alkaline phosphatase

MANAGEMENT:

1. Supportive

  • acute management of fungal infections
  • genetic counselling

 

 

Pediatric Database - MYELOPEROXIDASE DEFICIENCY

Pediatric Organization - Pedbase [at] Gmail.com