Phagocyte disorders — branching viva

Opening stem

A four-year-old boy presents with a staphylococcal liver abscess; in the past year he has had a Serratia pneumonia and a granulomatous gingivitis. His neutrophil count is normal, and his maternal uncle died in childhood from recurrent infection. The examiner asks: take me through how you reach the diagnosis, confirm it, and manage this child — and be prepared to branch. ^[4]

Branch 1 — The diagnosis and the organism cluster

Examiner: What is the single most informative clue, and why does the neutrophil count not reassure you? ^[4]

The organism list is the clue. Staphylococcus aureus and Serratia marcescens are members of the CGD cluster of catalase-positive organisms — alongside Burkholderia cepacia complex, Nocardia, and Aspergillus — which thrive when the phagocyte respiratory burst fails. The diagnosis is chronic granulomatous disease until proven otherwise. The neutrophil count is normal because in CGD the cells are made and they arrive at the infection in normal numbers; they simply cannot kill catalase-positive organisms. A normal neutrophil count never excludes CGD. The granulomatous gingivitis and the family history of an affected maternal uncle (X-linked inheritance) reinforce the diagnosis. ^{[4] [5]}

Branch 2 — The confirmatory test

Examiner: How do you confirm it, and what result do you expect? ^[4]

The decisive test is the dihydrorhodamine (DHR) 123 flow cytometry assay, which quantifies the oxidative burst after phorbol myristate acetate stimulation. Dihydrorhodamine fluoresces when oxidised, and the flow cytometer measures the fluorescence shift. In X-linked CGD (CYBB / gp91phox) the fluorescence is virtually absent — a flat histogram. In the autosomal recessive p47phox (NCF1) form it is reduced but present, a mosaic pattern reflecting residual oxidase activity in a subpopulation. The DHR assay has replaced the older nitroblue tetrazolium slide test because it is faster, quantitative, and distinguishes the X-linked from the autosomal recessive pattern. Genetic testing with a targeted panel confirms the molecular diagnosis. ^[4]