[PAGID] XLP testing

[Tamara Pozos]

Hello all - I am writing for advice re: genetic testing for severe EBV/XLP-like illness - (brother of my patient had a similar syndrome at 22 months, and there is a 3rd unaffected brother).  Specifically, are there other tests in addition to SH2D1A, (also ?XIAP) and if there is one particular lab that is recommended for this testing? Any other suggestions?

Clinical story in brief: previously well 6 year old boy with rapid onset of high fever, massive hepatosplenomegaly, nephritis, pleural effusions severe enough that PICU for respiratory concerns.  Multiple IgMs to viruses/Mycoplasma were positive,  so when I met him I sent PCRs: EBV 95K,CMV neg. Heme/onc also involved for concern of HLH, no lymph node or bone marrow biopsies were done.  Given concerns of rapid progression, I treated him a few days with gancyclovir and he improved rapidly.  Followup EBV level was 1500, stopped GCV.  One the day of discharge, he developed disseminated rash that very much resembled the amox rash seen with mono.

When I saw him last week in followup, rash was nearly faded, HSM and LAD had resolved.  I rechecked viral load and it rebounded somewhat, total CD3# continues to increase, Bcells lower so I am presuming that it's Bcell EBV tropism in this case.  Kid continues afebrile and to feel well.

The affected brother was 22 months when he went through this, also developed a rash in the recovery stage, and is now 9 years old. 

Thanks so much! Patient is coming back to see me in a few days.
Tamara Pozos, MD PhD



Details of labs, if one is interested. 
7/29/09
 	VCA Aby- IgG NEGATIVE
 	VCA Aby- IgM POSITIVE
 	EBNA Aby NEGATIVE &
 	CMV IgG NEGATIVE &
 	CMV IgM POSITIVE &
 	
 08/01/09 07:00 	
 	Ferritin 429 ng/mL (H) (Ref. Range 7 - 142)
 	Interleukin-2 Receptor >6500 U/mL & (H)

 08/02/09 20:30 		
 	Triglycerides 136 mg/dL (H) (Ref. Range 0 - 103)

 08/03/09 08:29 	
 	CD3+ Absolute 3,897 /uL (H) (Ref. Range 700 - 2,900)
 	CD4+/CD3+ Absolute 906 /uL (Ref. Range 400 - 1,500)
 	CD8+/CD3+ Absolute 2,723 /uL (H) (Ref. Range 180 - 1,000)
 	CD19+ Absolute 309 /uL (Ref. Range 200 - 800)
 	CD16+56+/CD3- Absolute 417 /uL (Ref. Range 100 - 800)
 	CD4:CD8 Ratio 0.33 (L) (Ref. Range 0.83 - 2.19)
 
 EBV Copies per mL 92,000
 	
 08/03/09 11:35 	
 	NK Function See Comments &
 	Chemistry Reports- scanned Chemistry Reports- scanned
  
 	IgM 182.0 mg/dL & (Ref. Range 46 - 197)
 	IgA 138.0 mg/dL & (Ref. Range 33 - 234)
 	IgG Subclass 1 1,009 mg/dL & (H) (Ref. Range 292 - 816)
 	IgG Subclass 2 126 mg/dL & (Ref. Range 83 - 513)
 	IgG Subclass 3 74 mg/dL & (Ref. Range 8 - 111)
 	IgG Subclass 4 51 mg/dL & (Ref. Range 1 - 121)
 	IgG 1,260 mg/dL & (H) (Ref. Range 608 - 1,229)
 	IgE 402.0 IU/mL & (H) (Ref. Range 0 - 90)

 	Ferritin 1,334 ng/mL (H) (Ref. Range 7 - 142)
  

 08/04/09 19:08 	
 	CMV by PCR- CMPC None Detected &

 08/07/09 08:16 	
 	Ferritin 1,400 ng/mL (H) (Ref. Range 7 - 142)
 
 	EBV Copies per mL 1,500 &
 Gancyclovir stopped	
  
Discharged home with rash developing, fever resolved after rash peaked.

Seen in followup 08/10/09, clinically very well 	
 	CD3+ Absolute 6,541 /uL (H) (Ref. Range 700 - 2,900)
 	CD4+/CD3+ Absolute 2,109 /uL (H) (Ref. Range 400 - 1,500)
 	CD8+/CD3+ Absolute 4,080 /uL (H) (Ref. Range 180 - 1,000)
 	CD19+ Absolute 100 /uL (L) (Ref. Range 200 - 800)
 	CD16+56+/CD3- Absolute 1,142 /uL (H) (Ref. Range 100 - 800)
 	CD4:CD8 Ratio 0.52 (L) (Ref. Range 0.83 - 2.19)
 
 	EBV Copies per mL 5,500
 	


Tamara Pozos, MD PhD
Pediatric Infectious Diseases and Immunology 
Children's Hospitals and Clinics of Minnesota 
Mail Stop 70-504 
Garden View Building, 3rd Floor 
345 Smith Avenue North 
St. Paul, MN  55102 
tamara.pozos at childrensmn.org 
651-220-6444 (office)
651-220-6293 (desk/voicemail)
612-589-7976 (pager)


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