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Blood, 1 August 2002, Vol. 100, No. 3, pp. 1026-1030
PHAGOCYTES
Deletion of leucine 61 in glucose-6-phosphate
dehydrogenase leads to chronic nonspherocytic anemia, granulocyte
dysfunction, and increased susceptibility to infections
Robin van Bruggen,
José M. Bautista,
Theoni Petropoulou,
Martin de
Boer,
Rob van Zwieten,
Felíx Gómez-Gallego,
Bernd H. Belohradsky,
Nico G. Hartwig,
David Stevens,
Philip J. Mason, and
Dirk Roos
From the Central Laboratory of the Netherlands Blood
Transfusion Service (CLB), the Laboratory for Experimental and Clinical
Immunology and the Emma Children's Hospital, both of the Academic
Medical Center, University of Amsterdam, The Netherlands; Department of
Biochemistry and Molecular Biology IV, University Complutense de
Madrid, Spain; Dr von Haunerschen Kinderspital, Ludwig Maximilians
Universität, München, Germany; Sophia Children's Hospital,
University Hospital Rotterdam, Erasmus Medical Center, The Netherlands;
and Department of Haematology, Imperial College School of Medicine,
Hammersmith Hospital, London, United Kingdom.
In this study the blood cells of 4 male patients from 2 unrelated
families with chronic nonspherocytic anemia and recurrent bacterial infections were investigated. The activity of
glucose-6- phosphate dehydrogenase (G6PD) in the red blood cells and
in the granulocytes of these patients was below detection level.
Moreover, their granulocytes displayed a decreased respiratory burst
upon activation. Sequencing of genomic DNA revealed a novel 3-base pair (TCT) deletion in the G6PD gene, predicting the deletion of a
leucine at position 61. The mutant G6PD protein was undetectable by
Western blotting in the red blood cells and granulocytes of these
patients. In phytohemagglutinin-stimulated lymphocytes the G6PD protein
was present, but the amount of G6PD protein was strongly diminished in
the patients' cells. Purified mutant protein from an Escherichia
coli expression system showed decreased heat stability and
decreased specific activity. Furthermore, we found that the messenger
RNA of G6PD180-182delTCT is unstable, which may contribute
to the severe G6PD deficiency observed in these patients. We propose
the name "G6PD Amsterdam" for this new variant.
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