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A new case of IPEX receiving bone marrow transplantation

Bone Marrow Transplantation volume 35, pages 1033–1034 (2005)Cite this article

At 4 months old, a male infant was admitted to hospital because of intractable secretory diarrhea and repeated episodes of sepsis. At admission, the child appeared malnourished (body weigh 4180 g, <3rd percentile) and with a widespread exfoliative ichtyosiform dermatitis. Duodenal biopsy showed villous atrophy and flattened mucosa. Serum IgG, IgA, IgM were normal, but IgE were elevated (763 kU/ml). A high titer (1 : 320) of antinuclear antibodies, and antibodies against insulin, glutamic acid decarboxylase (GAD-65) and enterocytes were found, leading to the hypothesis of immunodysregulation, polyendocrinopathy, entheropathy X-linked (IPEX) syndrome.1 Genetic analysis of Foxp3, the causative gene of IPEX,2, 3 did not show any mutation in the coding region of the gene, but markedly reduced levels of Foxp3 mRNA (as low as 32% of control subjects) were demonstrated by real-time PCR. A mutation (deletion) in the promoter region, as shown by PCR amplification, was identified about 6600 bp upstream from the start codon, suggesting that this mutation might account for the defective Foxp3 mRNA expression. IPEX is an X-linked disorder characterized by multiple autoimmune manifestations, including various combinations of severe entheropathy, type I diabetes mellitus, hypothyroidism, eczema and development of autoantibodies with onset in early infancy.3 Immunosuppressive treatment may attenuate or delay the clinical course, but continuous administration of corticosteroids and/or cyclosporine often leads to drug toxicities.3 Although partial engraftment after bone marrow transplantation (BMT) in the scurfy mouse, that is the equivalent of human IPEX, is sufficient to rescue the animals and to prevent fatal outcome,4 prior attempts at BMT in three children affected by IPEX were ultimately not successful.2, 5

In our patient, clinical remission and disappearance of autoantibodies were obtained by immunosuppressive treatment with high doses of corticosteroids (10 mg/kg of methylprednisolone per day for 2 days followed by 2 mg/kg of methylprednisolone per day and oral cyclosporine A at 5 mg/kg per day). At 2 months after discharge, upon reduction of corticosteroids dosage, the patient presented again with growth failure, eczema and diarrhea. Therefore, at 1 year of age, he was considered for BMT from his healthy, 4 years old, HLA-identical sister. The conditioning regimen consisted of intravenous fludarabine (30 mg/m2/day), from day –13 to day –10, oral busulphan (5 mg/kg/day from day −9 to day −6), intravenous cyclophosphamide (50 mg/kg/day from day −5 to day −2) and anti-T-lymphocyte globulin (2.5 mg/kg/day from day −5 to day −4). A total of 7.85 × 106 CD34+ cells/kg, including 50 × 106 CD3+ cells/kg were infused.

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Acknowledgements

The study was funded in part by PF2003 from Min-Salute to LDN and RB, Telethon Italia Grant No. GGP0485 to RB, and NIH Grant HD17427 to HO.

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Authors and Affiliations

  1. Department of Pediatrics, Istituto di Medicina Molecolare ‘Angelo Nocivelli’, University of Brescia, C/o Spedali civili, I-25125, Brescia, Italy

    E Mazzolari, C Forino, C D'Ippolito, A Lanfranchi, R Badolato & L D Notarangelo

  2. ‘Ospedale dei Bambini ‘Vittore Buzzi’ Milano’, Italy

    M Fontana

  3. Department of Pediatrics, Washington University, Seattle, USA

    E Gambineri & H Ochs

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  1. E Mazzolari
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  2. C Forino
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Mazzolari, E., Forino, C., Fontana, M. et al. A new case of IPEX receiving bone marrow transplantation. Bone Marrow Transplant 35, 1033–1034 (2005). https://doi.org/10.1038/sj.bmt.1704954

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