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Journal of Tropical Pediatrics Advance Access published online on January 19, 2008
Journal of Tropical Pediatrics, doi:10.1093/tropej/fmm119
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© The Author [2008]. Published by Oxford University Press. All rights reserved. For Permissions, please email: journals.permissions@oxfordjournals.org

Biliary Cirrhosis in a Child with Inherited Interleukin-12 Deficiency

Anoop S. Pulickala, Sophie Hambletonb, Martin J. Callaghana, Catrin E. Moorea, Jon Gouldingc, Anna Goodsalld, Richard Barettoe, David A. Lammase, Suzanne T. Andersond, Michael Levinf and Andrew J. Pollarda

aDepartment of Paediatrics, University of Oxford, CCVTM, Churchill Hospital, Oxford OX3 7LJ, UK
bDepartment of Pediatrics, Columbia University College of Physicians & Surgeons, 650 W. 168th Street, New York, NY 10032, USA
cThe Institute of Genetics, University of Nottingham, Queen's Medical Centre, Nottingham NG7 2UH
dDepartment of Paediatrics and Wellcome Centre for Clinical Tropical Medicine, Imperial College London, Norfolk Place, London W2 1PG
eMRC Centre for Immune Regulation, Division of Immunity and Infection, The Medical School, The University of Birmingham, Edgbaston B15 2TT
fBrighton and Sussex Medical School, University of Sussex, Brighton, East Sussex BN1 9PX, UK

Correspondence: Dr Anoop S. Pulickal, Department of Paediatrics, University of Oxford, Centre for Clinical Vaccinology and Tropical Medicine, Churchill Hospital, Oxford OX3 7LJ, UK. E-mail < anoop.sebastian{at}paediatrics.ox.ac.uk>.


  Abstract

Interleukin-12 (IL-12) is a key cytokine in the defense against intracellular bacteria notably Mycobacteria and Salmonella species. We report a case of disseminated mycobacterial infection, following BCG vaccination, in a child who later developed tuberculosis. Functional tests and a novel diagnostic polymerase chain reaction (PCR) assay, revealed a loss-of-function deletion in the IL12 gene. Analysis of samples from the parents and siblings of the patient indicated an autosomal recessive inheritance pattern with varying degrees of phenotypic expression in identical genotypes. Interferon-{gamma} (IFN-{gamma}) therapy was associated with marked clinical improvement. Biliary cirrhosis, a hitherto unreported complication of IL-12 deficiency, developed later and required liver transplantation. A defect in the IL-12–IFN-{gamma} pathway should be suspected in patients presenting with multiple, repeated or persistent infection with intracellular bacteria. The diagnostic work-up and the immuno-genetic assay described here can aid in the quick and reliable diagnosis of IL-12 deficiency resulting from genetic defects and its subsequent management.

Key Words: BCG • biliary cirrhosis • cytokine • deficiency • IL-12 • interferon-{gamma} • Mycobacteria • tuberculosis


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[Abstract] [Full Text] [PDF]


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