[CIS-PAGID] Leucopenia with no monocytes and low B cells

[Seppänen Mikko]

Hi,

I  tend to agree with Kate that GATA2 is a strong suspect, B-, NK- and monocytopenia being the most consistent findings, along with hypocellular myelodysplasia  (neutropenia thus caused by the intrinsic stem cell defect and clinically thus pt getting aphtae?). Have You checked his parents and siblings, whether any of them have the same blood count findings? Any of the relatives having problems with papillomaviruses, NTM mycobacteria, lungs (pulmonary alveolar proteinosis), myelodysplasia? Did the patient have any signs of mild dyserythropoiesis in BM samples? Lymphedema?

Immunologic phenotype thus would best(?) be consistent with DCML/MonoMAC either caused by GATA-2 or by yet an unknown gene? 

From Italy, considering that fresh samples are needed that reach the laboratory within 24h, You would need to check where You can send viable samples:
1) in Europe, You might want to contact Matthew Collin and Sophie Hambleton in Newcastle, they could check the patient's blood (level of flt3 ligand), marrow and eventually fibroblast lines? 
2) in the US, Steve Holland/NIH  might be of help? (and in Philadelphia/Kate and Jordan; I did not quite get the expression "in the barin", Kate?)

In summary, like Kate, I would eventually aim to sequence GATA2...

Yours 

Mikko Seppänen, Helsinki, Finland


________________________________________
Lähettäjä: pagid-bounces at list.clinimmsoc.org [pagid-bounces at list.clinimmsoc.org] käyttäjän Sullivan, Kathleen [sullivak at mail.med.upenn.edu] puolesta
Lähetetty: 21. syyskuuta 2011 20:46
Vastaanottaja: pagid at list.clinimmsoc.org
Aihe: Re: [CIS-PAGID] Leucopenia with no monocytes and low B cells

Maybe I have GATA2 on the barin- but this seems like one who should be sequenced as well.


On Sep 21, 2011, at 1:39 PM, Eleonora Gambineri wrote:

Dear all,
I would like your inputs on the case below:
8y/o male
Past medical history:
•         recurrent otitis and pharyngitis until adenoidectomy (4 yo)
•         4yo: chickenpox with normal course
•         Since 6yo: episodes of aphthous stomatitis every2-3 months, sometimes associated with fever.

•         August 2010: CBC -> leucopenia
Laboratory work up:
October 2010:
•         WBC: 3300/μL, Neutrophils 26.6% (absolute value: 877/ μL) Monocyte 0%
•         CMV, EBV, Toxoplasmosis: negative
•         Celiac disease screening: negative
•         ANA, ENA, pANCA: negative
•         Anti-neutrophils Ab: negative
•         Immunoglobulins: within normal range

•         Lymphocyte subsets:  B cells 9% (absolute value 240/ μL), T cells CD3+ 87% (av: 2310), T cells CD3+CD4+ 48% (av: 1270/ μL), T cells CD3+CD8+ 22% (av: 580/ μL), NK cells 4% (110/ μL)
Genuary 2011

•         Bone Marrow Aspiration:  hypocellular for the age of the patient, dysmyelopoiesis
May 2011: fever + arthritis
•         WBC: 3200/μL, Neutrophils 21.7% (absolute value: 690/μL) Monocyte 0%, Hemoglobin 10.3 g/dl, platelet  153000/μL
•         Parvovirus B19 blood PCR: positive
•         Lymphocyte subsets:  B cells 7% (absolute value 176/ μL), T cells CD3+ 92% (av: 2480/ μL), T cells CD3+CD4+ 54% (av: 1457/ μL), T cells CD3+CD8+ 27% (av: 742/ μL), NK cells 1% (39/ μL)

•         CD3+TCRαβ+CD4-CD8- (DNT cells): 1,3% of CD3+lymphocyte
Bone Marrow Aspiration:
•         Normal cellularity with decreased myeloid series
•         TERC gene and TINF2 gene: no mutations
•         FISH chromosome 7, 8 LSI 21 (21q22.13-q22.2): no chromosomal abnormalities

•         Parvovirus  B19 PCR: positive
July 2011:
•         WBC: 2470/μL, Neutrophils 22.8% (absolute value: 563/μL) Monocyte 0.4%, Hemoglobin 13 g/dl, platelet  138000/μL
•         Parvovirus B19 blood PCR: negative

•         Clinically well

 Currently ongoing: FAS induced apoptosis assay, B memory cell phenotype, specific antibodies (i.e. anti-pneumococcus, anti-tetanus)


Any thoughts/suggestions is really appreciated!

Thanks.

BEst wishes,

Eleonora

*******************************************************************
Dott.ssa Eleonora Gambineri
Ricercatore Universitario

Universita' degli Studi di Firenze, Dipartimento di Scienze per la Salute della Donna e del Bambino
Ospedale Pediatrico "Anna Meyer", Dipartimento di Oncoematologia-Unità TMO
Viale Gaetano Pieraccini, 24
50139 FIRENZE
Tel 055 5662405 (ufficio)
       055 5662606 (reparto T.M.O.)
Fax 055 4221012
e-mail: eleonora.gambineri at unifi.it<mailto:eleonora.gambineri at unifi.it>; e.gambineri at meyer.it<mailto:e.gambineri at meyer.it>

Eleonora Gambineri, MD
Researcher/Assistant Professor

University of Florence, Department of Sciences for Woman and Child's Health
"Anna Meyer" Children's Hospital, Department of Haem/Onc-BMT Unit
Viale Gaetano Pieraccini, 24
50139 FIRENZE
ITALY
Tel +39 055 5662405 (office)
       +39 055 5662606 (BMT Unit)
Fax +39 055 4221012
e-mail: eleonora.gambineri at unifi.it<mailto:eleonora.gambineri at unifi.it>; e.gambineri at meyer.it<mailto:e.gambineri at meyer.it>
********************************************************************






Kate Sullivan, MD PhD
Professor of Pediatrics
ARC 1216 Immunology CHOP
3615 Civic Center Blvd.
Philadelphia, PA 19104
(p) 215-590-1697
(f) 267-426-0363