[CIS PIDD] [cis-pidd] work up and therapeutic advise for patient with possible Omenn Syndrome
Chinn, Ivan Kingyue
Ivan.Chinn at bcm.edu
Mon Sep 29 23:01:16 EDT 2014
The diagnosis of SCID vs. complete DiGeorge can be very difficult to distinguish, as even Louise herself will tell you. Nonetheless, I would recommend contacting her sooner rather than later – and certainly before waiting for all of the test results return. The thymus transplant waiting list can often be quite long…
- Ivan
From: Dylan Mordaunt [mailto:d.a.mordaunt at gmail.com]
Sent: Monday, September 29, 2014 9:21 PM
To: CIS-PIDD
Cc: Prescott Atkinson, M.D.
Subject: Re: [cis-pidd] work up and therapeutic advise for patient with possible Omenn Syndrome
Dear Carsten and Allison,
PGM3 is not within the regions of homozygosity (http://www.ccs.miami.edu/cgi-bin/ROH/ROH_analysis_tool.cgi). Unfortunately it looks like transferrin isoforms are normal in PGM3-CDG, but abnormalities can be detected on serum N-glycan analysis- the only clinical lab I am aware of that offers this in the US is the Mayo Clinic. Without a history of consanguinity, homozygosity mapping doesn't tend to be very useful. If there is a history of consanguinity, it might be worth asking the array lab to re-send the coordinates with the >3Mb limit removed and enter them into the linked website.
In the absence of a deletion on microarray, a multigene panel and exon array would probably be the quickest way to verify your diagnosis. Many of these labs will expedite testing in your circumstances-
https://www.nextgxdx.com/apps/search/#/compare?tC=%5B%2255e70ae2341945748a1ea2f100229461%22%5D
http://www.ncbi.nlm.nih.gov/gtr/tests/501119/
Kind regards,
Dylan
Clinical and Metabolic Genetics Fellow
South Australian Clinical Genetics Service
Dylan Mordaunt
Mobile: + 61 468 516 283
Email: d.a.mordaunt at gmail.com<mailto:d.a.mordaunt at gmail.com>
On 29 September 2014 19:18, Dr. Carsten Speckmann <carsten.speckmann at uniklinik-freiburg.de<mailto:carsten.speckmann at uniklinik-freiburg.de>> wrote:
Were mutations in PGM3 considered in these "non-22q11 / DiGeorge like" patients?
The phenotype of PGM3 deficiency is probably highly variable and includes SCID-like disease with complex skeletal malformations: http://www.ncbi.nlm.nih.gov/pubmed/24931394
The mouse model also has renal and testical abnormalities.
Dr Norton: Your patients has large regions of homozygosity, including chr 6 (maybe you want to check, whether PGM3 is within this region)
Kind regards, Carsten Speckmann
Dr. med. Carsten Speckmann
Funktionsoberarzt/Consultant Immunologist
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<mailto:carsten.speckmann at uniklinik-freiburg.de>
web: www.cci.uniklinik-freiburg.de<http://www.cci.uniklinik-freiburg.de/>
Am 28.09.14 19:25, schrieb Prescott Atkinson, M.D.:
Hi Allison: I neglected to mention that our patient also is negative for the 22q11.2 deletion, as have been all of the five or so complete DiGeorge patients we have had at UAB over the past 20 years. Other details: Complex congenital anomalies with right aortic arch/left ligamentum (vascular ring), absent left kidney, absent left testis, spinal anomalies, dextrocardia, absent left 4th rib. He has had a negative CGH array. As I mentioned, analysis of his TCR alpha-beta gene utilization for signs of clonality showed multiple bands c/w oligoclonality. After consultation with Dr. Markert, we have been treating our patient with cyclosporine and IVIG. About the time he had his vascular ring divided on July 11th preparatory to transfer to Duke, his respiratory status deteriorated and he has not been able to be weaned off the ventilator - no clear infectious etiology identified as yet - has been treated with multiple courses of antibacterial and anti fungal antibiotics and bactrim prophylaxis. He does have enterovirus persistent in his stool.
Over the past 3 weeks in an effort to wean him in the absence of any clear pathogen, he has been treated with IV solumedrol and most recently with a single dose of ATGAM. He had developed severe peripheral edema which resolved with solumedrol but his respiratory status didn't change. His circulating B cells had disappeared over the past two months and they have rebounded to normal numbers after the ATGAM supporting our suspicion that they were being targeted by autoreactive T cells. Unfortunately, near ablation of his T cells with ATGAM, while triggering a pretty significant amount of acute inflammation, has not yet resulted in sufficient improvement in his respiratory status for him to be extubated, although he has weaned a little on his FiO2. I am still hopeful that at least part of his respiratory problems are due to his autoreactive T cells and that he will yet improve, perhaps with another dose of ATGAM.
Prescott
T. Prescott Atkinson, MD PhD, Professor and Director
Division of Pediatric Allergy, Asthma & Immunology
University of Alabama at Birmingham
Tel: 205-939-9072
Fax: 205-975-7080
________________________________
From: Jyonouchi, Soma C [JYONOUCHI at email.chop.edu<mailto:JYONOUCHI at email.chop.edu>]
Sent: Saturday, September 27, 2014 3:21 PM
To: CIS-PIDD
Subject: Re: [cis-pidd] work up and therapeutic advise for patient with possible Omenn Syndrome
B cell numbers were normal for your patient so less likely to be rag/Artemis. You could also think about excluding omenn SCID due to gamma chain/jak3 since nk cells were on the low side
Soma
Sent from my iPhone
On Sep 27, 2014, at 3:58 PM, "Prescott Atkinson, M.D." <PAtkinson at peds.uab.edu<mailto:PAtkinson at peds.uab.edu>> wrote:
I agree - we have a similar patient who Louise has agreed to transplant but we have been having a lot of trouble getting him stable enough for transfer. TCR clonality studies returned showing oligoclonality.
T. Prescott Atkinson, MD PhD, Professor and Director
Division of Pediatric Allergy, Asthma & Immunology
University of Alabama at Birmingham
Tel: 205-939-9072
Fax: 205-975-7080
________________________________
From: Kate Sullivan [sullivak at mail.med.upenn.edu<mailto:sullivak at mail.med.upenn.edu>]
Sent: Saturday, September 27, 2014 2:48 PM
To: CIS-PIDD
Subject: Re: [cis-pidd] work up and therapeutic advise for patient with possible Omenn Syndrome
Sounds like atypical digeorge syndrome. See Louise markerts paper.
Kate Sullivan
Sent from my iPhone
On Sep 27, 2014, at 3:42 PM, "Norton, Allison" <allison.norton at Vanderbilt.Edu<mailto:allison.norton at Vanderbilt.Edu>> wrote:
Hi, I have a 5 month old male patient with a history of tetralogy of Fallot s/p BT shunt, choledochal cyst s/p excision, unilateral renal agenesis, with multiple chromosome homozygosities( FISH negative 22q11.2) with a phenotype concerning for Omenn's syndrome (diffuse erythrodermic peeling rash, progressive alopecia, splenomegaly, high IgE levels (1664), persistant eosinophilia (4000) and 99% CD4+CD45RO+ memory T cells with no naive T cells on T cell phenotyping). He was admitted initially for rhinovirus and required ventilatory support about one month ago, then developed daily fevers and noted to have the progressive rash and eosinophilia. He is rhinovirus free now but quickly outgrowing his shunt and requiring oxygen. He has normal number of B cells, slight T cell lymphocytosis, normal immunoglobulins except for high IgE, and low response to Con A using 3H-thymidine but normal response to PHA and pokeweed. He had no response to diptheria, tetanus, or pneumococcal vaccine. He had essentially normal bone marrow biopsy with trilineage hematopoiesis, no overt dysplasia and negative FISH for PDGFRB. He was negative for maternal cells in identity study. Skin biopsy revealed Epidermal acanthosis and mixed dermal inflammation
with scattered multinucleated giant cells and evidence of granuloma formation. His initial CXR revealed very little thymus and operative report from cardiac surgery states that there was essentially no thymus present.
Pertinant labs as follows:
CMV/ EBV quantification negative
Vitamin B12: 1268
Tryptase 4.5
IgA 18 IgM 87 IgG 308 IgE 1664
LYMPHS (ABS) <https://star69.mc.vanderbilt.edu/cgi-bin/sp/graphs.cgi?-i:037262227.vumc:037262227.ohc+-load+037262227+B&Tsubsets+Normal+LYMPAB> 4.55 x10(3)/mcL (2.50-9.80)
PAN T CD3 % <https://star69.mc.vanderbilt.edu/cgi-bin/sp/graphs.cgi?-i:037262227.vumc:037262227.ohc+-load+037262227+B&Tsubsets+Normal+CD3%25> 80* % (58-69)
CD3 #/CUMM <https://star69.mc.vanderbilt.edu/cgi-bin/sp/graphs.cgi?-i:037262227.vumc:037262227.ohc+-load+037262227+B&Tsubsets+Normal+CD3%23> 3640* #/cumm (1700-3600)
T HELPER CD4 % <https://star69.mc.vanderbilt.edu/cgi-bin/sp/graphs.cgi?-i:037262227.vumc:037262227.ohc+-load+037262227+B&Tsubsets+Normal+CD4%25> 58* % (30-50)
T HELPER CD4 #/CUMM <https://star69.mc.vanderbilt.edu/cgi-bin/sp/graphs.cgi?-i:037262227.vumc:037262227.ohc+-load+037262227+B&Tsubsets+Normal+CD4%23> 2639 #/cumm (1000-2800)
CD8(CD3+)/CD45 % <https://star69.mc.vanderbilt.edu/cgi-bin/sp/graphs.cgi?-i:037262227.vumc:037262227.ohc+-load+037262227+B&Tsubsets+Normal+CD8/3%25> 22 % (18-32)
CD8(CD3+)/CD45 #/CUMM <https://star69.mc.vanderbilt.edu/cgi-bin/sp/graphs.cgi?-i:037262227.vumc:037262227.ohc+-load+037262227+B&Tsubsets+Normal+CD8/3%23> 1001 #/cumm (800-1500)
CD16+56 (NK) % <https://star69.mc.vanderbilt.edu/cgi-bin/sp/graphs.cgi?-i:037262227.vumc:037262227.ohc+-load+037262227+B&Tsubsets+Normal+56%2B16%25> 3* % (8-17)
CD16+56 #/CUMM <https://star69.mc.vanderbilt.edu/cgi-bin/sp/graphs.cgi?-i:037262227.vumc:037262227.ohc+-load+037262227+B&Tsubsets+Normal+56%2B16%23> 136* #/cumm (200-700)
PAN B CD19 % <https://star69.mc.vanderbilt.edu/cgi-bin/sp/graphs.cgi?-i:037262227.vumc:037262227.ohc+-load+037262227+B&Tsubsets+Normal+CD19%25> 16* % (19-31)
CD19 #/CUMM <https://star69.mc.vanderbilt.edu/cgi-bin/sp/graphs.cgi?-i:037262227.vumc:037262227.ohc+-load+037262227+B&Tsubsets+Normal+CD19-%23> 728 #/cumm (500-1500)
FISH IMPRESSION:
No evidence of a deletion within the 22q11.2 Deletion syndrome critical region (see comments).
FISH KARYOTYPE:
nuc ish 22q11.2(HIRAx2),22q13.3(ARSAx2)
No maternal DNA was detected using multiplex fluorescent PCR for 15 independently segregating polymorphic loci and one gender-specific locus, Amelogenin (AMEL). Amplicons of varying lengths were detected by capillary electrophoresis and analyzed.
Microarray result:
Increased regions of homozygosity detected.
Microarray interpretation:
SNP chromosomal microarray analysis (CMA) of this patient's peripheral blood sample demonstrated no copy number changes of known clinical significance.
Several large regions of homozygosity (approximately 3 Mb or larger) were detected, encompassing >2.4% of this patient's genome. This result is not diagnostic of a specific condition, but raises the possibility of a recessive disorder for which the causative gene is located within these regions. We recommend genetic counseling for the parents of this patient. Regions of homozygosity are listed below.
chr1:47218172-57275564
chr2:95341387-98816010
chr3:1424744-6211233
chr3:73398682-80384839
chr3:48456768-52506491
chr3:31092370-34407028
chr5:70671938-79480620
chr6:184718-3466022
chr8:39230311-39386952
chr8:46913605-52048415
chr11:63142527-67465968
chr14:106329183-106717343
chr16:34449594-34765444
chr16:68829020-72276824
chr16:31133409-35220544
chr16:494410-6263633
chr22:38832511-42296703
T cell phenotyping was sent to Mayo lab and revealed total CD4 lymphocytosis. Practically all the T cells in the blood were in the memory T cell subsets with complete absence of naive CD4+ and CD8+ T cells. Almost all the T cells are the activated phenotype, expressing MHC class II-Hla DR. 99% CD4+CD45RO+ memory T cells with no naive T cells.
Pending studies include Rag 1/2, artemis mutations and chimerism studies. We are also planning to send TRECS, repeat lymphocyte proliferation to Pha using flow via Mayo clinic, TCR vbeta via spectrotyping, CD4 RTE for thymic emigrants, Anti CD3 panel.
We need help with this diagnosis and therapy. He has phenotypic features of both DiGeorge syndrome (TOF, unilateral renal agenesis, choledochal cyst) and Omenn syndrome(rash, splenomegaly, high IgE, eosinophilia, no naive T cells). So the question is does he have Omenn syndrome and how could I differentiate that from an atypical DiGeorge? Would he require a thymus transplant, bone marrow transplant, or neither?
We are concerned about waiting too long before transplanting, if he requires this, because he is rapidly outgrowing his shunt and his eosinophilia continues to rise (today 8000), in addition to the infection risk.
Thank you for your time with this difficult patient.
Allison Norton, MD
Pediatric Allergy and Immunology
Vanderbilt University
Nashville, TN
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On 29 September 2014 19:18, Dr. Carsten Speckmann <carsten.speckmann at uniklinik-freiburg.de<mailto:carsten.speckmann at uniklinik-freiburg.de>> wrote:
Were mutations in PGM3 considered in these "non-22q11 / DiGeorge like" patients?
The phenotype of PGM3 deficiency is probably highly variable and includes SCID-like disease with complex skeletal malformations: http://www.ncbi.nlm.nih.gov/pubmed/24931394
The mouse model also has renal and testical abnormalities.
Dr Norton: Your patients has large regions of homozygosity, including chr 6 (maybe you want to check, whether PGM3 is within this region)
Kind regards, Carsten Speckmann
Dr. med. Carsten Speckmann
Funktionsoberarzt/Consultant Immunologist
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<mailto:carsten.speckmann at uniklinik-freiburg.de>
web: www.cci.uniklinik-freiburg.de<http://www.cci.uniklinik-freiburg.de>
Am 28.09.14 19:25, schrieb Prescott Atkinson, M.D.:
Hi Allison: I neglected to mention that our patient also is negative for the 22q11.2 deletion, as have been all of the five or so complete DiGeorge patients we have had at UAB over the past 20 years. Other details: Complex congenital anomalies with right aortic arch/left ligamentum (vascular ring), absent left kidney, absent left testis, spinal anomalies, dextrocardia, absent left 4th rib. He has had a negative CGH array. As I mentioned, analysis of his TCR alpha-beta gene utilization for signs of clonality showed multiple bands c/w oligoclonality. After consultation with Dr. Markert, we have been treating our patient with cyclosporine and IVIG. About the time he had his vascular ring divided on July 11th preparatory to transfer to Duke, his respiratory status deteriorated and he has not been able to be weaned off the ventilator - no clear infectious etiology identified as yet - has been treated with multiple courses of antibacterial and anti fungal antibiotics and bactrim prophylaxis. He does have enterovirus persistent in his stool.
Over the past 3 weeks in an effort to wean him in the absence of any clear pathogen, he has been treated with IV solumedrol and most recently with a single dose of ATGAM. He had developed severe peripheral edema which resolved with solumedrol but his respiratory status didn't change. His circulating B cells had disappeared over the past two months and they have rebounded to normal numbers after the ATGAM supporting our suspicion that they were being targeted by autoreactive T cells. Unfortunately, near ablation of his T cells with ATGAM, while triggering a pretty significant amount of acute inflammation, has not yet resulted in sufficient improvement in his respiratory status for him to be extubated, although he has weaned a little on his FiO2. I am still hopeful that at least part of his respiratory problems are due to his autoreactive T cells and that he will yet improve, perhaps with another dose of ATGAM.
Prescott
T. Prescott Atkinson, MD PhD, Professor and Director
Division of Pediatric Allergy, Asthma & Immunology
University of Alabama at Birmingham
Tel: 205-939-9072
Fax: 205-975-7080
________________________________
From: Jyonouchi, Soma C [JYONOUCHI at email.chop.edu<mailto:JYONOUCHI at email.chop.edu>]
Sent: Saturday, September 27, 2014 3:21 PM
To: CIS-PIDD
Subject: Re: [cis-pidd] work up and therapeutic advise for patient with possible Omenn Syndrome
B cell numbers were normal for your patient so less likely to be rag/Artemis. You could also think about excluding omenn SCID due to gamma chain/jak3 since nk cells were on the low side
Soma
Sent from my iPhone
On Sep 27, 2014, at 3:58 PM, "Prescott Atkinson, M.D." <PAtkinson at peds.uab.edu<mailto:PAtkinson at peds.uab.edu>> wrote:
I agree - we have a similar patient who Louise has agreed to transplant but we have been having a lot of trouble getting him stable enough for transfer. TCR clonality studies returned showing oligoclonality.
T. Prescott Atkinson, MD PhD, Professor and Director
Division of Pediatric Allergy, Asthma & Immunology
University of Alabama at Birmingham
Tel: 205-939-9072
Fax: 205-975-7080
________________________________
From: Kate Sullivan [sullivak at mail.med.upenn.edu<mailto:sullivak at mail.med.upenn.edu>]
Sent: Saturday, September 27, 2014 2:48 PM
To: CIS-PIDD
Subject: Re: [cis-pidd] work up and therapeutic advise for patient with possible Omenn Syndrome
Sounds like atypical digeorge syndrome. See Louise markerts paper.
Kate Sullivan
Sent from my iPhone
On Sep 27, 2014, at 3:42 PM, "Norton, Allison" <allison.norton at Vanderbilt.Edu<mailto:allison.norton at Vanderbilt.Edu>> wrote:
Hi, I have a 5 month old male patient with a history of tetralogy of Fallot s/p BT shunt, choledochal cyst s/p excision, unilateral renal agenesis, with multiple chromosome homozygosities( FISH negative 22q11.2) with a phenotype concerning for Omenn's syndrome (diffuse erythrodermic peeling rash, progressive alopecia, splenomegaly, high IgE levels (1664), persistant eosinophilia (4000) and 99% CD4+CD45RO+ memory T cells with no naive T cells on T cell phenotyping). He was admitted initially for rhinovirus and required ventilatory support about one month ago, then developed daily fevers and noted to have the progressive rash and eosinophilia. He is rhinovirus free now but quickly outgrowing his shunt and requiring oxygen. He has normal number of B cells, slight T cell lymphocytosis, normal immunoglobulins except for high IgE, and low response to Con A using 3H-thymidine but normal response to PHA and pokeweed. He had no response to diptheria, tetanus, or pneumococcal vaccine. He had essentially normal bone marrow biopsy with trilineage hematopoiesis, no overt dysplasia and negative FISH for PDGFRB. He was negative for maternal cells in identity study. Skin biopsy revealed Epidermal acanthosis and mixed dermal inflammation
with scattered multinucleated giant cells and evidence of granuloma formation. His initial CXR revealed very little thymus and operative report from cardiac surgery states that there was essentially no thymus present.
Pertinant labs as follows:
CMV/ EBV quantification negative
Vitamin B12: 1268
Tryptase 4.5
IgA 18 IgM 87 IgG 308 IgE 1664
LYMPHS (ABS) <https://star69.mc.vanderbilt.edu/cgi-bin/sp/graphs.cgi?-i:037262227.vumc:037262227.ohc+-load+037262227+B&Tsubsets+Normal+LYMPAB> 4.55 x10(3)/mcL (2.50-9.80)
PAN T CD3 % <https://star69.mc.vanderbilt.edu/cgi-bin/sp/graphs.cgi?-i:037262227.vumc:037262227.ohc+-load+037262227+B&Tsubsets+Normal+CD3%25> 80* % (58-69)
CD3 #/CUMM <https://star69.mc.vanderbilt.edu/cgi-bin/sp/graphs.cgi?-i:037262227.vumc:037262227.ohc+-load+037262227+B&Tsubsets+Normal+CD3%23> 3640* #/cumm (1700-3600)
T HELPER CD4 % <https://star69.mc.vanderbilt.edu/cgi-bin/sp/graphs.cgi?-i:037262227.vumc:037262227.ohc+-load+037262227+B&Tsubsets+Normal+CD4%25> 58* % (30-50)
T HELPER CD4 #/CUMM <https://star69.mc.vanderbilt.edu/cgi-bin/sp/graphs.cgi?-i:037262227.vumc:037262227.ohc+-load+037262227+B&Tsubsets+Normal+CD4%23> 2639 #/cumm (1000-2800)
CD8(CD3+)/CD45 % <https://star69.mc.vanderbilt.edu/cgi-bin/sp/graphs.cgi?-i:037262227.vumc:037262227.ohc+-load+037262227+B&Tsubsets+Normal+CD8/3%25> 22 % (18-32)
CD8(CD3+)/CD45 #/CUMM <https://star69.mc.vanderbilt.edu/cgi-bin/sp/graphs.cgi?-i:037262227.vumc:037262227.ohc+-load+037262227+B&Tsubsets+Normal+CD8/3%23> 1001 #/cumm (800-1500)
CD16+56 (NK) % <https://star69.mc.vanderbilt.edu/cgi-bin/sp/graphs.cgi?-i:037262227.vumc:037262227.ohc+-load+037262227+B&Tsubsets+Normal+56%2B16%25> 3* % (8-17)
CD16+56 #/CUMM <https://star69.mc.vanderbilt.edu/cgi-bin/sp/graphs.cgi?-i:037262227.vumc:037262227.ohc+-load+037262227+B&Tsubsets+Normal+56%2B16%23> 136* #/cumm (200-700)
PAN B CD19 % <https://star69.mc.vanderbilt.edu/cgi-bin/sp/graphs.cgi?-i:037262227.vumc:037262227.ohc+-load+037262227+B&Tsubsets+Normal+CD19%25> 16* % (19-31)
CD19 #/CUMM <https://star69.mc.vanderbilt.edu/cgi-bin/sp/graphs.cgi?-i:037262227.vumc:037262227.ohc+-load+037262227+B&Tsubsets+Normal+CD19-%23> 728 #/cumm (500-1500)
FISH IMPRESSION:
No evidence of a deletion within the 22q11.2 Deletion syndrome critical region (see comments).
FISH KARYOTYPE:
nuc ish 22q11.2(HIRAx2),22q13.3(ARSAx2)
No maternal DNA was detected using multiplex fluorescent PCR for 15 independently segregating polymorphic loci and one gender-specific locus, Amelogenin (AMEL). Amplicons of varying lengths were detected by capillary electrophoresis and analyzed.
Microarray result:
Increased regions of homozygosity detected.
Microarray interpretation:
SNP chromosomal microarray analysis (CMA) of this patient's peripheral blood sample demonstrated no copy number changes of known clinical significance.
Several large regions of homozygosity (approximately 3 Mb or larger) were detected, encompassing >2.4% of this patient's genome. This result is not diagnostic of a specific condition, but raises the possibility of a recessive disorder for which the causative gene is located within these regions. We recommend genetic counseling for the parents of this patient. Regions of homozygosity are listed below.
chr1:47218172-57275564
chr2:95341387-98816010
chr3:1424744-6211233
chr3:73398682-80384839
chr3:48456768-52506491
chr3:31092370-34407028
chr5:70671938-79480620
chr6:184718-3466022
chr8:39230311-39386952
chr8:46913605-52048415
chr11:63142527-67465968
chr14:106329183-106717343
chr16:34449594-34765444
chr16:68829020-72276824
chr16:31133409-35220544
chr16:494410-6263633
chr22:38832511-42296703
T cell phenotyping was sent to Mayo lab and revealed total CD4 lymphocytosis. Practically all the T cells in the blood were in the memory T cell subsets with complete absence of naive CD4+ and CD8+ T cells. Almost all the T cells are the activated phenotype, expressing MHC class II-Hla DR. 99% CD4+CD45RO+ memory T cells with no naive T cells.
Pending studies include Rag 1/2, artemis mutations and chimerism studies. We are also planning to send TRECS, repeat lymphocyte proliferation to Pha using flow via Mayo clinic, TCR vbeta via spectrotyping, CD4 RTE for thymic emigrants, Anti CD3 panel.
We need help with this diagnosis and therapy. He has phenotypic features of both DiGeorge syndrome (TOF, unilateral renal agenesis, choledochal cyst) and Omenn syndrome(rash, splenomegaly, high IgE, eosinophilia, no naive T cells). So the question is does he have Omenn syndrome and how could I differentiate that from an atypical DiGeorge? Would he require a thymus transplant, bone marrow transplant, or neither?
We are concerned about waiting too long before transplanting, if he requires this, because he is rapidly outgrowing his shunt and his eosinophilia continues to rise (today 8000), in addition to the infection risk.
Thank you for your time with this difficult patient.
Allison Norton, MD
Pediatric Allergy and Immunology
Vanderbilt University
Nashville, TN
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