[CIS-PAGID] 22q12.3 defect and poor wound healing

[Larkin, Allyson]

Dr. Verbsky, 
Thank you for your reply. It is a heterozygous defect.  We will send out the functional tests.
Allyson

________________________________________
From: pagid-bounces at list.clinimmsoc.org [pagid-bounces at list.clinimmsoc.org] on behalf of Verbsky, James [jverbsky at mcw.edu]
Sent: Friday, December 02, 2011 3:26 PM
To: pagid at list.clinimmsoc.org
Subject: Re: [CIS-PAGID] 22q12.3 defect and poor wound healing

Allyson

Is the defect a deletion (heterozygous??).  It is unlikely that there is a complete defect in RAC2 since there is pus.  RAC1 and 2 are somewhat redundant.  The reason the other cases were described is that the mutation was a dominant negative.  Its possible that there is a more subtle defect (for example..if haplo insufficient..perhaps signaling is low but not absent).  A few thoughts of functional tests that we found abnormal in such a case (who clearly had a wound healing defect)

1) DHR for CGD..be sure to include fMLP as a stimulant(we do this at MCW but others may as well).
2) Neutrophil migration (National Jewish does this).

Both of these are abnormal in the RAC2 cases, but perhaps in your case the defect will be a bit more subtle.


James

-----Original Message-----
From: pagid-bounces at list.clinimmsoc.org [mailto:pagid-bounces at list.clinimmsoc.org] On Behalf Of Larkin, Allyson
Sent: Friday, December 02, 2011 1:15 PM
To: <pagid at list.clinimmsoc.org>
Subject: [CIS-PAGID] 22q12.3 defect and poor wound healing

Dear Colleagues:


We have a 7 week old female with a 22q12.3 defect who has had poor wound healing after cardiothoracic surgery.  Immunology was asked to comment on MSSA bacteremia and mediastinitis. On review of the literature, defects in 22q13.1 are associated with "neutrophil immunodeficiency syndrome" caused by mutation in the RAC2 gene (OMIM 602049).  Her clinical history is outlined below. We would appreciate any thoughts related to her clinical presentation and her 22q12.3 defect; specifically related to the possibility of a phagocytic/neutrophil disorder.

*        Born at term to non consanguineous parents with hemihypertrophy and capillary vascular malformations. Also had a portal venous thrombosis (? Line related).

*        Known prenatal cardiac anomalies (double inlet left ventricle, hypoplastic right ventricle, large bulboventricular foreman, malposed great vessels, sub-pulmonic stenosis and valvar pulmonic stenosis)

*        Had a Blalock-Taussig shunt procedure 6 weeks ago (day of life 4). Operative report commented on presence of a thymus.

*        Discharged to home but readmitted with fever.

*        Taken back to the operating room and large amount of pus found on exploration. Wound cultures positive for MSSA and gram stain showed many neutrophils.  Blood cultures also positive for MSSA.

*        No omphalitis or delayed cord separation.

*        A genetic workup found a defect on the 22q12.3 region of the long arm of chromosome 22.

*        Family history significant for XLA in a second cousin.

*        Laboratory studies: (CBCs do not show persistent leukocytosis or lymphopenia, NOBA and CH50 pending)
IgA                                                                    21 Milligrams/deciliter
IgG                                                                    446 Milligrams/deciliter
IgM                                                                   41 Milligrams/deciliter
% T-Cells (CD3)                                               74 %  High
Total T-Cells (CD3)                                        4606 /cumm  High
% Helper Cells (CD4)                                    59 %  High
Total Helper Cells (CD4)                              3683 /cumm  High
% Suppressor Cells (CD8)                            14 %  Low
Total Suppressor Cells (CD8)                      894 /cumm
% B-Cells (CD19)                                         18 %  Low
Total B-Cells (CD19)                                     1143 /cumm
% NK Cells (CD16/CD56)                              7 %
Total NK Cells (CD16/CD56)                        419 /cumm
Helper/Suppressor Ratio                             4.12   High

                              Karyotype 22q12.3(32,191,531-532,537,463)x1.


Allyson Larkin, MD
Children's Hospital of Pittsburgh