[CIS PIDD] advise on an 11mo old male

[Keller, Michael D]

This case doesn't sound leaky as much as fairly typical SCID.  CHH (RMRP) runs in the Amish community.  AK2 is on chromosome 1, and is associated with profound lymphopenia.  

Have you looked for maternal engraftment (given the IgA spike)?

Mike
________________________________________
From: pagid-bounces at list.clinimmsoc.org [pagid-bounces at list.clinimmsoc.org] On Behalf Of Chong, Hey [hey.chong at chp.edu]
Sent: Friday, June 22, 2012 2:34 PM
To: 'pagid at list.clinimmsoc.org'
Subject: [CIS PIDD] advise on an 11mo old male

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