[PAGID] Follow up on baby with hypogamma and Sweet's

[Conley, Mary-Ellen]

thanks John and Paul
 - the absence of any CD19 + cells in the bone marrow goes against the diagnosis of XLA or mu heavy chain or any of the autosomal recessive agamma involved in signaling through the pre-BCR.  Patients with these disorders (and patients with RAG defects) have normal numbers of CD34/CD19+ cells (pro-B cells).  As you noted, patients with myelodysplasia or other disorders of hematopoiesis sometimes present with infection and absent B cells.  These patients have no CD19+ B cells, like your patient.  The persistent thrombocytopenia goes along with this diagnosis as well.  I agree that it is important to explore the possibility of malignancy.
Mary Ellen





Mary Ellen Conley, MD
Department of Immunology/ Mail Stop 351
St. Jude Children's Research Hospital
262 Danny Thomas Place
Memphis, TN 38105-3678
FAX  901-595-3977
TEL  901-595-2576



________________________________
From: pagid-bounces at list.clinimmsoc.org [mailto:pagid-bounces at list.clinimmsoc.org] On Behalf Of John Ziegler
Sent: Monday, April 27, 2009 2:10 AM
To: pagid at list.clinimmsoc.org
Subject: [PAGID] Follow up on baby with hypogamma and Sweet's


This is an update on our now six week old boy with agammaglobulinaemia and markedly decreased B-cells who presented with neonatal Sweet's Syndrome, whose details we posted on PAGID a couple of weeks ago.  Thank you for your inputs which have helped greatly with directing our investigations.

We have now managed to obtain a bone marrow aspirate (no trephine) and it appears he may have underlying juvenile myelomonocytic leukaemia (JMML), but without any associated cytogenetic abnormalities.  He continues to have thrombocytopenia with platelet counts of c. 70,000 and an evolving anaemia with Hb falling to 84.

In terms of his B-cells, while the initial report suggested that he may have had c. 1% B-cells in his peripheral blood, subsequent analysis (while on steroids) failed to identify any.  This was in keeping with flow cytometry on the bone marrow which demonstrated completely absent B-cells as outlined on the appended report.   We are currently awaiting btk mutation analysis.

Following up on the previous concerns about possible partial RAG mutations we looked at T-cell V* analysis, which demonstrated no abnormalities of the T-cell subsets present. We have also requested chimerism studies to ensure these are not abnormally engrafted maternal cells, and the results of that test are pending.  We performed basic T-cell function (PHA), which was absent, however there were problems with the handling of the sample and we are awaiting a repeat.  He is not behaving like a SCID to date.

Our thoughts:
Initially we wondered whether this might be btk deficiency however there is now a feeling amongst the involved clinicians that the haematological abnormalities may be primary.  Certainly JMML could explain many of the findings effecting liver, spleen, bone marrow and skin (Sweet's has been reported with JMML) and the very large monocytosis at presentation favours this diagnosis.   Also, while JMML has not itself been reported as being associated with immune deficiency, it is closely associated, and shares cytogenetic abnormalities (e.g. monosomy 7) with myelodysplastic syndrome, a disease which has been linked to PID.

Kleebsabai Srivannaboon, Mary-Ellen Connolly et al Hypogammaglobulinemia and Reduced Numbers of B-Cells in Children with Myelodysplastic Syndrome.

Journal of Pediatric Hematology/Oncology, Vol. 23, No. 2, February 2001
While our patient is very different from the three patients mentioned in that paper, in particular having a much more severe presentation, we wondered whether our boy had an earlier or more severe "hit" which has caused him to present more severely.

We would be very interested in your further ideas about this intriguing baby.
[No%20AttachName]




Paul Gray and John Ziegler
Department of Immunology & Infectious Diseases
Sydney Children's Hospital
High St., Randwick NSW 2031
Australia
T: (02) 93821515
F: + 61 + 2 93821580
E: j.ziegler at unsw.edu.au

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