[CIS PIDD] [cis-pidd] Hyper IgM syndrome?

[CIS-PIDD]

CTLA4 looked at in detail?
We have initially missed patients with heterozygous whole exon or whole
gene deletions in CTLA4 gDNA.
Same applies for comp het deletions in LRBA...
Best, Bodo

****************************************
Univ.-Prof. Dr. med. B. Grimbacher
 
Scientific-Director
CCI-Center for Chronic Immunodeficiency
UNIVERSITÄTSKLINIKUM FREIBURG
Tel.: 0761 270-77731  Fax: -77744
Breisacherstraße 115, 79106 Freiburg
bodo.grimbacher at uniklinik-freiburg.de
www.uniklinik-freiburg.de/cci
 
and 
 
Consultant Immunologist
Institute of Immunity & Transplantation
Dept of Immunology
Royal Free Hospital
UNIVERSITY COLLEGE LONDON
Pond Street
London NW3 2QG
b.grimbacher at ucl.ac.uk

www.centreforimmunodeficiency.com




Am 12/07/16 17:33 schrieb "CIS-PIDD" unter <cis-pidd at lists.clinimmsoc.org>:

>Dear colleagues,
>
>I am writing to ask you for your opinion about a challenging case.
>
>Our patient is a 14yo boy who was healthy until the age of 9yo when he
>had two episodes of ITP episodes treated with steroids, IVIG, and
>rituximab.  Then this year, he was hospitalized for fever with ITP,
>Coombs+ anemia, weight loss, pulmonary nodules on chest CT, and
>significant splenomegaly.  He was treated with IV antibiotics, and slowly
>improved, without any immuno suppression.  Immunoglobulin levels
>demonstrated IgA <5, IgG <25, IgM 1357 (last rituxtimab dose 4 years
>ago). Lymph node biopsy demonstrated follicular hyperplasia with
>predominant primary follicles (no polarization), and increased IgM+
>lymohoplasmacytic cells.  No evidence of malignancy nor plasmactyosis.
>BM biopsy demonstrated mildly hypo cellular marrow (70%) with active
>trilineage hematopoiesis.  Normal T cell, NK, and total B cell numbers,
>but decreased (close to zero) isotope switched B cells (CD19+CD38+IgM-,
>CD19+CD27+IgM-IgD-).  Normal Treg cell numbers (foxp3 stain).  Lymphocyte
>stimulation with normal mitogen and tetanus response (mildly decreased
>ConA, but otherwise normal). A battery of infectious studies all yielded
>negative results (EBV, CMV, bacterial cx, PCP, fungal cx, mycobacterial
>cx).  
>
>WES sent at this point, and started on IgG replacement, with no other
>immunomodulator. Splenomegaly significantly improved, no fevers, normal
>CBC, still some fatigue, slowly regaining weight.   3 months later,
>repeat immunoglobulins demonstrate IgG 207, IgA<10, IgM 340.  WES results
>(GeneDx) demonstrate het mutations for PKLR (pyruvate kinase deficiency),
>VPS13B (Cohen syndrome), and ANK1 (hereditary spherocytosis).  Given his
>IgM has almost normalized with only IgG supplementation, this is unlikely
>HIGM I think. CD40/40L,UNG, AID, IKBa coverage was pretty good. NEMO
>coverage not so good (26%).  He however does not many any of the physical
>exam features, and does not have any GI issues.  None of the mutations
>founds are consistent with his phenotype, and they are only heterozygous.
> 
>
>I¹m facing a diagnostic dilemma at this point.  My original thought of
>HIGM seems to have gone out the window, any other suggestions?
>
>Thanks,
>
>Elena Hsieh, MD
>Department of Immunology and Microbiology
>Department of Pediatrics, Division of Allergy and Immunology
>University of Colorado, Denver
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