A 5-year-old girl presented with three episodes of otomastoiditis caused by Candida species. The last episode was complicated with persistent Staphylococcus Aureus cervical lymph node abscess. She was treated with transtympanic drains, mastoidectomy and long-term antibiotics and antifungal therapy, as well as drainage and curettage for the cervical abscess.
Immunological work-up consisted of standard blood analysis, lymphocyte proliferation test and respiratory burst assay. Subsequently, based on the results, genetic testing for chronic granulomatous disease (CGD) (CYBA, CYBB, NCF1, NCF2 and NCF4) and myeloperoxidase deficiency (MPO) was performed, as well as histochemical staining of leukocytes.
General immunological testing was normal, except for a very weak response in the respiratory burst assay (<10% at multiple testing), suggesting CGD. However, gene testing for CGD was negative. Subsequently, MPO expression on neutrophils was absent. Analysis of the MPO gene showed a homozygous splice site mutation in intron 11 (c.2031-2A>C), producing an abnormal precursor without the enzymatic activity. Subsequent familial screening revealed the same mutation in her younger brother presenting with recurrent oral candidiasis.
MPO deficiency should be considered in patients with recurrent Candida infections and reduced respiratory burst. It is the most frequent congenital phagocytic cell disorder leading to an increased risk of infections with Candida and Aspergillus species. The majority of patients are asymptomatic or only exhibit minor infections, but some will develop major infections, especially in presence of concomitant diabetes mellitus. Our patient was successfully treated with a prophylactic dose of fluconazole.