[PAGID] ? Possible SCID

[Abraham, Roshini S., Ph.D.]

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 8/10-->10/16, 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 12/24-->1/15 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:

 

1.	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. 
2.	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. 
3.	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. 
4.	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. 
5.	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 <mailto: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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