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Successful long-term correction of autosomal recessive hyper-IgE syndrome due to DOCK8 deficiency by hematopoietic stem cell transplantation.

Abstract
Autosomal dominant hyper-IgE syndrome (AD-HIES), characterised by eczema, increased susceptibility to skin and lung infections, elevated IgE and skeletal abnormalities is associated with heterozygous STAT3 mutations. The autosomal recessive variant (AR-HIES) has similar immunological findings but mainly lacks extraimmune manifestations. Several AR-HIES patients have recently been shown to harbour mutations in the gene for dedicator of cytokinesis 8 (DOCK8). Here, we present the long-term outcome of a girl having received a hematopoietic stem cell graft for an at that time genetically undefined combined immunodeficiency associated with severe eczema, multiple food allergies, excessively elevated serum IgE levels and eosinophilia. She was recently found to carry a homozygous nonsense mutation in the DOCK8 gene. HSCT resulted in complete immunological correction, even though mixed donor chimerism occurred. Clinically, the outcome was characterised by disappearance of skin manifestations and severe infections, improvement of pulmonary function and constant decline of IgE levels. Outcome in untransplanted DOCK8 deficient patients is poor because of frequent life-threatening infections, CNS bleeding and infarction, and increased susceptibility to malignancy. This argues for early curative therapeutic approaches, supported by this report of successful long-term outcome after HSCT.
AuthorsT C Bittner, U Pannicke, E D Renner, G Notheis, F Hoffmann, B H Belohradsky, U Wintergerst, M Hauser, B Klein, K Schwarz, I Schmid, M H Albert
JournalKlinische Pàˆdiatrie (Klin Padiatr) Vol. 222 Issue 6 Pg. 351-5 (Nov 2010) ISSN: 1439-3824 [Electronic] Germany
PMID21058221 (Publication Type: Case Reports, Journal Article)
Copyright© Georg Thieme Verlag KG Stuttgart · New York.
Chemical References
  • DOCK8 protein, human
  • Guanine Nucleotide Exchange Factors
  • STAT3 Transcription Factor
  • STAT3 protein, human
Topics
  • Child
  • Child, Preschool
  • Consanguinity
  • DNA Mutational Analysis
  • Female
  • Follow-Up Studies
  • Guanine Nucleotide Exchange Factors (deficiency, genetics)
  • Hematopoietic Stem Cell Transplantation
  • Humans
  • Job Syndrome (genetics, therapy)
  • STAT3 Transcription Factor (genetics)

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