[CIS PIDD] advise on an 11mo old male

[Dr. Carsten Speckmann]

Hey,

making the diagnosis in leaky SCID can be quite a challenge.
Kerstin Felgentreff reviewed the published and our experience with this 
last year - http://www.ncbi.nlm.nih.gov/pubmed/21664875
In summary assessment of T cell numbers, PHA response, g/d T cells and 
naive T cells are very helpful.
No parameter has a 100% sensitivity but most patients will show changes 
in 2/4 of these items.
We therefore usually recommend to work up these items thoroughly in kids 
like yours.
We also currently use these parameter as entry criteria for a 
prospective study on these conditions - www.pcid-study.org

What confuses me a bit when looking at your case is the discrepancy of 
almost nl naive Ts but low TRECs (which are pobably measured at 
different time points?). Is there a chance that you can obtain the 
original newborn screening card (in case Amish children are screened?) 
to look for TREC levels at birth? Low levels there will certainly point 
towards a disturbed thymic output, although in some CID they might be 
normal. In those case determination of KRECs might also be useful (also 
if specific abs are present):
http://www.ncbi.nlm.nih.gov/pubmed/22578972
http://www.ncbi.nlm.nih.gov/pubmed/22664165

Although lab parameters of your case seem to point towards a CID, the 
infection pattern is not so typical and you probably also screened for 
chronic viral diseases (EBV, CMV, Adeno), which I assume are negative? 
The results of the burst assays are also odd and I would sort this out 
(ideally in an infection free period if possible). FTT and sepsis due to 
pseudomonas could also point towards a TLR defect.
http://www.ncbi.nlm.nih.gov/pubmed/21734245
http://www.ncbi.nlm.nih.gov/pubmed/21057262

I agree with all the others that sorting out the underlying diagnosis 
should not delay a timely preparaton of SCT.

Carsten




Am 22.06.12 20:34, schrieb Chong, Hey:

> Dear all,

> We  have a difficult case and I would love to hear some thoughts and 

> advice.

> My main questions are :

> Is this CID/SCID?

> Would you transplant or send for further genetic testing first?

> The case:

> 11mo FT amish male born of consanguineous parents (second cousins) 

> with history of FTT frequent AOM, no history of rashes, no LAD, no HSM

> hospitalized for respiratory distress at 10mo, found to have 

> pseudomonas and haemophilus positive blood cultures  and 

> metapneumovirus +respiratory culture.

> He was pancytopenic thought to be due to sepsis.  Thrombocytopenia 

> resolved but he continued to be anemic and lymphopenic with most 

> recent lymphocyte count of 550.  Pan low lymphocyte subsets **_% 

> T-Cells (CD3) _87, _(CD3) _143; _%(CD4) _9; _(CD4) _15; %_(CD8) _72; 

> _(CD8) _118; _%(CD19) _9; _(CD19) _15; _% (CD16/CD56) _2; _Total 

> (CD16/CD56) _n 3

> He also has IgG 200-300, IgM 34-55 and a rising IgA as high as 652.  

> Dx with IgA kappa monoclonal gammopathy,

> He had +titers to tetanus vaccine.  We did flow cytometry looking at 

> naïve T cell markers told that of his lympocytes, these were the 

> percentages:

> _CD3+ _56

> _CD3+/CD4+ _10

> _CD3+/CD45RA+ _92

> _CD4+/CD45RA+ _54

> _CD4+/CD45RA+/CD62L+ _54

> We recently sent for TRECS with values all below 7 copies/uL after 

> repeating test on two different samples.  He was very lymphopenic at 

> the time.

> Mitogen assay done as well:

> _Max Prolif PWM, CD45 _n 5.5

> _Max Prolif PWM, CD3 _n 6.2

> _Max Prolif PWN, CD19 _n 6.7

> _Max Prolif PHA, CD45 _n 25.2

> _Max Prolif PHA, CD3 _n 28.4

> He also initially had abnormal neutrophil oxidative burst assay with 

> no activity, repeat showed population with and without activity.

> Sweat test normal, he was bronched and negative for Pneumocystis

> Do you think it is possible that he has a leaky SCID or could this be 

> something else that we are missing?  What do we make of the IgA 

> gammopathy?  He had a bone marrow biopsy that was not suggestive of 

> cancer but did show some hemophagocytosis, however he did not meet dx 

> criteria for HLH.

> ADA and PNP assay sent to Duke, normal.

> genetic SNP array found 16p11.2 duplication, associated with autism 

> and developmental delay.  Also showed significant homozygosity  in 

> regions of Ch1,2 and 10, and I am getting more information on these 

> specific genes soon.

> Any thoughts at all would be greatly appreciated.

> Thank you very much

> Hey Jin Chong

> Hey Jin Chong MD PhD

> Assistant Professor of Pediatrics

> Division of Pulmonary Medicine, Allergy & Immunology

> Children's Hospital of Pittsburgh of UPMC

> One Children's Hospital Drive

> 4401 Penn Avenue

> Pittsburgh, PA 15224

> tel 412-692-7885

> fax 412-692-8499

>



-- 
Dr. med. Carsten Speckmann
Facharzt
Zentrum fuer Kinderheilkunde und Jugendmedizin
Centrum fuer Chronische Immundefizienz - CCI
Universitaet Freiburg
Mathildenstr. 1
79106 Freiburg
Germany

phone: +49 (0)761-270 43010
mail: carsten.speckmann at uniklinik-freiburg.de
web: www.cci.uniklinik-freiburg.de


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