[PAGID] ? Possible SCID

[Kathleen E. Sullivan]

This is very bizarre but I had a patient with EXACTLY that  
phenotype.  She/he was worked up extensively and no gene defect was  
found but eventually her autoimmune disease became nearly  
uncontrollable and she received a BMT.  She has done very well since  
then.

Kate
Kathleen E. Sullivan MD PhD
Chief, Division of Allergy and Immunology
Professor of Pediatrics
The Children's Hospital of Philadelphia
(p) 215-590-1697
(f) 267-426-0363


On Feb 20, 2009, at 5:16 PM, Abraham, Roshini S., Ph.D. wrote:


> On behalf of Dr. Aly Mageed:

>

>

> Dear PAGID colleagues,

>

> I am seeking some input/advice with regards to the following case:

>

> Patient is a 7 month old WF (DOB 6/30/08), half a non identical  

> twin, who presented at 6 weeks with severe Coomb’s + AIHA (Warm +  

> IgG and C3) (Hgb of 2.5 gm) and WBC was 32,000 while ALC was 5,491  

> (stayed 1700-2470 for the next 12 days and later she had only 2-7%  

> lymphs with ALC of around 500) and had to be emergently exchange  

> transfused with non irradiated blood. No earlier CBC’s are  

> available. She was then started on steroids 3mg/kg/day and weekly  

> Vincristin (got 16 doses). Prednisone was tapered (was on 3mg/kg  

> from 8/10à10/16, 2/k till 11/26, 0.7 mg/kg till 12/24). She then  

> presented on Dec 24/2008 with PCP pneumonia despite Pentamidine Px.  

> PCP was treated successfully with Bactrim 20mg/k from 12/24à1/15  

> with re-increase of Pred. to 2.2mg/kg until12/30, 1.5/k until 1/ 4  

> and 1mg/k till 1/9, 0.7mg/kg until 1/9 and 0.25 mg/k until 2/1/09.

>

> Lymphocyte subpopulations were done on January 16 and showed low  

> WBC in general at 1700 (was on Pred. and Bactrim as above) ALC was  

> 417, CD19=15, CD3= 94, CD4= 38, CD8= 46 and CD16/56= 304. She  

> started having a skin rash and diarrhea with FTT. Rash disappeared  

> upon increasing steroids to relapse upon its taper. Bx was  

> suggestive of mild GVHD in gut and skin (was under steroid and  

> cyclosporine) with CD4 and CD8 infiltration.

>

> While looking for XY to rule out TA-GVHD we found out that she is  

> constitutionally XY with testicular feminization. The blood donor  

> was a male who is now undergoing STR analysis to R/O TA-GVHD. IgG  

> was 687, M= 97 on 9/25 (after IVIG therapy for AIHA) but IgG was  

> 180, M was 111 on 1/16 and IgG was 383 on 1/29. HIV is negative.  

> Mitogen stimulation was very low at 2-3% of NC (maximal cpm of  

> ~4000 on a background of 130 for PHA/ ConA) (but was on steroids/ 

> VCR as above).

>

> Repeat Lymph subpopulations on 2/10 showed WBC of 2,700, ALC = 355,  

> CD19=37, CD3= 215, CD 4=149, CD8= 63 and CD16/56 = 103. Last CBC  

> showed 3000 WBC and ALC = 780, on steroids.

>

> BM showed mild/moderate hypoplasia with marked lymphopenia.  

> Isohemagglutinin was low at 1:2, (she is O-). Gut and skin x  

> suggestive+/- GVHD changes on treatment.  PNP is unlikely with NL  

> uric acid and ADA-B level was NL. Genetic testing is pending for  

> RAG1/2, JAK-3, Artemis, IL2RG. Also, we did not find any XX cells  

> for possible maternal engraftment on skin biopsy or blood.  The  

> questions are:

>

> Do we have enough clinical evidence for a diagnosis of SCID without  

> having to wait for molecular diagnosis? She has a matched sib to  

> move to BMT right away.

> Or, is she having an iatrogenic immune deficiency caused by almost  

> a life long therapy with steroids/VCR which can cause lymphopenia,  

> and her leukopenia is Bactrim related? Her presentation with AIHA  

> is possible/rare with SCID and usually it is a late manifestation  

> rather than presenting Sx.

> Interestingly the testicular feminization gene is close to SCID on  

> the X chromosome. I am still looking for the donor STR markers in  

> her to R/O TA-GVHD.

> I will repeat the Mitogen Stimulation on only physiologic dose of  

> steroids and if low again move to BMT with or without gene proof.  

> We are also going to do array CGH and TREC/RTE analsysis for  

> evidence of thymic activity.

> The other question is would conditioning be appropriate with  

> recently reduced low NK cells as well?

>

> I would greatly appreciate any advice or comments on this  

> challenging case.

>

>

> Aly Mageed, MD, MBA

> Division Chief, Pediatric Blood & Marrow Transplant Program

> Director, Stem Cell Engineering Laboratory

> Helen DeVos Children's Hospital, Spectrum Health

> Associate Professor of Pediatrics, Michigan State University

> 100 Michigan street NE

> Grand Rapids, MI 49503

> MC#185

>

> (616)-391-3962

> aly.mageed at spectrum-health.org

>

>

>

>

> Roshini Sarah Abraham, Ph.D., D(ABMLI)

>

> Director

> Cellular and Molecular Immunology Laboratory

> Department of Laboratory Medicine and Pathology

> Hilton 210 e

> Mayo Clinic

> 200 1st St SW

> Rochester, MN-55905

> Ph: 507-266-9292

> Ph (Secy): 507-284-4055

> Fax: 507-266-4088

>

>


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