[CIS PIDD] advise on an 11mo old male

[Nicholas Rider]

Hi All,

The Amish have ADA deficiency (ADA c. 646 G>A), a hypomorphic RAG1 mutation which causes Omenn Syndrome (RAG1 c.2794A>G) and CHH (as previously mentioned; classic Finnish mutation RMRP A>G).  To date we don't know about any Amish with the IL7Ra mutation; however, this is found in the Mennonite populations (IL7R c. 2T>G) as well as a Zap 70 Kinase mutation (ZAP70 IVS4-11 G>A) to my knowledge.  

All Amish patients with CHH have the associated skeletal dysplasia which is evident by 10 months of age.  They also have a (frustratingly so)  highly variable immune phenotype that to date defies classification.  That being said, any laboratory finding is possible among the Amish with CHH.  

The Clinic for Special Children can assess for the above mentioned variants if you wish. 

Sincerely, 

Nick


Nicholas L. Rider, D.O.
Medical Art Allergy
Carlisle, PA

Clinic for Special Children
535 Bunker Hill Road
Strasburg, PA 17579
Ph:  717-687-9407
Fx:   717-687-9237
nrider at clinicforspecialchildren.org



On Jun 22, 2012, at 5:45 PM, Sullivan, Kathleen wrote:


> Amish have a founder mutation for IL-7Ra deficiency.  His T/B/NK phenotype isn't perfect but I would send it.  Remember that you don't need a mutation to move forward with BMT which is indicated for your patient.

> 

> On Jun 22, 2012, at 2:34 PM, Chong, Hey wrote:

> 

>>  

>> 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

>> 

>>  

>>  

>>  

> 

> Sullivan, Kathleen, MD PhD

> Professor of Pedaitrics

> Wallace Chair of Pediatrics

> Division of Allergy Immunology

> The Children's Hospital of Philadelphia

> ARC 1216 

> 3615 Civic Center Blvd

> Philadelphia, PA 19104

> sullivak at mail.med.upenn.edu

> 

> 

> 

> 


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