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Hyper IgM Syndrome: a Report from the USIDNET Registry

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Abstract

Purpose

The United States Immunodeficiency Network (USIDNET) patient registry was used to characterize the presentation, genetics, phenotypes, and treatment of patients with Hyper IgM Syndrome (HIGM).

Methods

The USIDNET Registry was queried for HIGM patient data collected from October 1992 to July 2015. Data fields included demographics, criteria for diagnosis, pedigree analysis, mutations, clinical features, treatment and transplant records, laboratory findings, and mortality.

Results

Fifty-two physicians entered data from 145 patients of ages 2 months to 62 years (median 12 years); 131 were males. Using patients’ age at last entry, data from 2072 patient years are included. Mutations were recorded for 85 subjects; 82 were in CD40LG. Eighteen subjects had non-X-linked HIGM. 40 % had a normal serum IgM and 15 %, normal IgA. Infections were reported for 91 %, with pulmonary, ear, and sinus infections being the most common. 42 % had Pneumocystis jirovecii pneumonia; 6 % had Cryptosporidium. 41 % had neutropenia. 78 % experienced non-infectious complications: chronic diarrhea (n = 22), aphthous ulcers (n = 28), and neoplasms (n = 8) including colon cancer, adrenal adenoma, liver adenocarcinoma, pancreatic carcinoid, acute myeloid leukemia, hepatoma, and, in a female with an autosomal dominant gain of function mutation in PIK3CD, an ovarian dysgerminoma. Thirteen patients had a hematopoietic marrow or stem cell transplant; three had solid organ transplants. Thirteen were known to have died (median age = 14 years).

Conclusions

Analysis of the USIDNET Registry provides data on the common clinical features of this rare syndrome, and in contrast with previously published data, demonstrates longer survival times and reduced gastrointestinal manifestations.

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Acknowledgments

This work was supported by the National Institutes of Health, AI 101093, AI-086037, AI-48693, T32-GM007280, The Jeffrey Modell Foundation, and the David S Gottesman Immunology Chair. We gratefully acknowledge the enthusiasm, expertise, and dedication of Tara Caulder, USIDNET Project Director, and Marla Goldsmith, USIDNET Registry Manager.

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Authors and Affiliations

  1. Icahn School of Medicine at Mount Sinai, New York, NY, USA

    Emily A. Leven, Patrick Maffucci & Charlotte Cunningham-Rundles

  2. Seattle Children’s Hospital Seattle, Seattle, WA, USA

    Hans D. Ochs

  3. Boehringer Ingelheim Pharmaceuticals, Inc., Ridgefield, CT, USA

    Paul R. Scholl

  4. Duke University School of Medicine, Durham, NC, USA

    Rebecca H. Buckley & Coleen K. Cunningham

  5. Children’s Memorial Hospital, Chicago, IL, USA

    Ramsay L. Fuleihan

  6. Boston Children’s Hospital, Harvard Medical School, Boston, MA, USA

    Raif S. Geha & Francisco A. Bonilla

  7. Rockefeller University, New York, NY, USA

    Mary Ellen Conley

  8. Children’s Hospital Los Angeles, Los Angeles, CA, USA

    Ronald M. Ferdman

  9. Miami Children’s Hospital, Miami, FL, USA

    Vivian Hernandez-Trujillo

  10. University of California San Francisco School of Medicine, San Francisco, CA, USA

    Jennifer M. Puck

  11. The Children’s Hospital of Philadelphia, Philadelphia, PA, USA

    Kathleen Sullivan

  12. Children’s Hospital of Michigan, Detroit, MI, USA

    Elizabeth A. Secord

  13. Montefiore Medical Center, Bronx, NY, USA

    Manish Ramesh

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  1. Emily A. Leven
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  2. Patrick Maffucci
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Corresponding author

Correspondence to Charlotte Cunningham-Rundles.

Additional information

*Additional USIDNET contributors: O-Neill Shigeoka, Ann; Brasher, George W; Chen, Karin; Derauf, Christian; Duplantier, John E; Greene, Jeffrey M; Rosen, Fred S; Schneider, Lynda C; Schuval, Susan; Winkelstein, Jerry A; Cleary, Thomas G; Day, Noorbibi K; Fikrig, Senih; Filipovich, Alexandra H; Gern, James E; Greaves, Kristen C; Hilman, Bettina C; Huttenlocher, Anna; Infante, Anthony J; Irani, Anne-Marie A; Jain, Ashish; Kobayashi, Roger H; Kosinski, S Mark; Lawton, Alexander R; Lederman, Howard M; McGeady, Stephen J; Menon, Prem K; Muskat, Mica; Pahwa, Savita; Patel C, Niraj; Reid, Tanya E; Saulsbury, Frank T; Slater, Jay E; Sleasman, John W; Suez, Daniel; Uygungil, Burcin; Venkat, Geeta; and Wong, Duane W

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Leven, E.A., Maffucci, P., Ochs, H.D. et al. Hyper IgM Syndrome: a Report from the USIDNET Registry. J Clin Immunol 36, 490–501 (2016). https://doi.org/10.1007/s10875-016-0291-4

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  • DOI: https://doi.org/10.1007/s10875-016-0291-4

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