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Severe X-linked chronic granulomatous disease in two unrelated females

European Journal of Pediatrics volume 166, pages 153–159 (2007)Cite this article

Abstract

Chronic granulomatous disease (CGD) is a rare primary immunodeficiency caused by mutations of one of the subunits of phagocyte reduced nicotinamide adenine dinucleotide phosphate (NADPH) oxidase leading to decreased or complete absence of neutrophil oxidative burst. We report the clinical and laboratory findings in two young unrelated females 14 and 9 years of age and natives of Tahiti and Reunion Islands, respectively, with severe X-linked granulomatous disease. In both cases, the infectious pattern was unusual, with convergent symptoms suggesting underlying mycobacterial infection. Functional analysis revealed low residual NADPH oxidase activity with about 5–10% of normal neutrophil population. De novo null mutations affecting the CYBB gene that encodes the gp91 protein were found in both cases in the heterozygous state (in patient 1, p.Arg130X in exon 5, and in patient 2, a novel insertion in exon 6, c.632_633insCATC). Methylation analysis confirmed that phenotype expression was linked to skewed X inactivation and showed that the de novo mutation arose on the maternally inherited chromosome in one case and on the paternally inherited chromosome in the other case. In conclusion, X-linked CGD carriers could therefore be at risk for severe infectious diseases depending on the skewed X inactivation pattern and the infectious context.

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Abbreviations

CGD:

Chronic granulomatous disease

ROS:

Reactive oxygen species

PMN:

Polymorphonuclear neutrophil

DCFH-DA:

Dichlorofluorescin diacetate

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Affiliations

  1. Service d’Immunologie Biologique, Hôpital Bichat-Claude Bernard, AP-HP, 46 rue Henri Huchard, 75018, Paris, France

    Sylvie Chollet-Martin & Anne Lopez

  2. Unité d’Immunologie Clinique, Centre Hospitalier Départemental Felix Guyon, Saint Denis de la Réunion, France

    Catherine Gaud

  3. Service de Biochimie Hormonale et Génétique, Hôpital Bichat-Claude Bernard, AP-HP, 75018, Paris, France

    Dominique Henry, Bernard Grandchamp & Bénédicte Gérard

  4. Service de Pédiatrie, Hôpital Saint Vincent de Paul, AP-HP, 75014, Paris, France

    Bertrand Stos & Dominique Gendrel

  5. Service d’Hématologie et d’Immunologie, Hôpital Bichat-Claude Bernard, AP-HP, 75018, Paris, France

    Jamel El Benna & Marie-Anne Gougerot-Pocidalo

  6. Unité d’Immunologie et d’Hématologie, Fédération de Pédiatrie, Hôpital Necker, AP-HP, 75006, Paris, France

    Gaëlle Chedevile

Authors
  1. Sylvie Chollet-Martin
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  2. Anne Lopez
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  3. Catherine Gaud
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  4. Dominique Henry
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  5. Bertrand Stos
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  6. Jamel El Benna
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  7. Gaëlle Chedevile
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  8. Dominique Gendrel
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  9. Marie-Anne Gougerot-Pocidalo
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  10. Bernard Grandchamp
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  11. Bénédicte Gérard
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Correspondence to Sylvie Chollet-Martin.

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Chollet-Martin, S., Lopez, A., Gaud, C. et al. Severe X-linked chronic granulomatous disease in two unrelated females. Eur J Pediatr 166, 153–159 (2007). https://doi.org/10.1007/s00431-006-0211-3

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  • DOI: https://doi.org/10.1007/s00431-006-0211-3

Keywords

  • Chronic granulomatous disease
  • Neutrophil
  • Oxidative burst
  • Infection
  • X-linked disease