Hyper IgM Syndrome: a Report from the USIDNET Registry - PubMed (original) (raw)

. 2016 Jul;36(5):490-501.

doi: 10.1007/s10875-016-0291-4. Epub 2016 May 17.

Patrick Maffucci 1, Hans D Ochs 2, Paul R Scholl 3, Rebecca H Buckley 4, Ramsay L Fuleihan 5, Raif S Geha 6, Coleen K Cunningham 4, Francisco A Bonilla 6, Mary Ellen Conley 7, Ronald M Ferdman 8, Vivian Hernandez-Trujillo 9, Jennifer M Puck 10, Kathleen Sullivan 11, Elizabeth A Secord 12, Manish Ramesh 13, Charlotte Cunningham-Rundles 14

Affiliations

Hyper IgM Syndrome: a Report from the USIDNET Registry

Emily A Leven et al. J Clin Immunol. 2016 Jul.

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.

Keywords: CD40/CD40L; Hyper IgM Syndrome; Primary immune deficiency; USIDNET.

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Figures

Fig. 1

Fig. 1

Patient ages

Fig. 2

Fig. 2

Immunoglobulin levels at time of diagnosis compared to age-adjusted reference ranges. Patients whose age was unknown at time of blood draw were considered according to the largest possible range of normal values

Fig. 3

Fig. 3

a. Reported sites of infection in all patients (n = 145). The asterisk indicates causal organisms of Hepatitis unknown. b. Incidence of infectious organisms in only those patients for whom clinical data for infection was available (n = 132; remaining 12 patients did not have data on infection)

Fig. 4

Fig. 4

Incidence of non-infectious complications. The asterisk indicates combined variable (see “clinical data” in Methods). The degree sign indicates that musculoskeletal does not include arthritis/ arthralgia. The plus sign indicates that dental/oral does not include aphthous ulcers

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