[CIS PIDD] [cis-pidd] 14 yo boy with myelodysplasia needing heart transplant.

Wed Jul 22 11:04:24 EDT 2015

Hi Dr Ylmaz.

Did you specifically check for GATA-2 deficiency?  Your case could be
suggestive for this diagnosis, because I notice B-Cell lymphopenia and
Myelodysplasia, recurrent infections, fungemia, even though there are no NK
deficiency. Any Monocytopenia? No Pulmonar Hypertension neither PAP?

I remember during my fellowship in Immunology in Montreal that the genetic
diagnosis was a real challenge for some cases.

Best regards.

JJ De Bruycker, MD
Emundston Regional Hospital, NB

On 22 July 2015 at 10:52, Yeşim Yılmaz Demirdağ <dryesimyilmaz at gmail.com>
wrote:

> Dear all,
> I would like to ask your opinion about a young boy with myelodysplasia
> since 2.5 yrs of age who developed congestive heart failure and is in need
> of a heart transplant. The question was about lymphopenia and recurrent
> infections and how this would impact immunosuppression if he gets the
> cardiac transplant. Below is the summary of his findings:
>
> 14 yo boy with:
>
> Persistent cytopenias (thrombocytopenia at 20-40K, mild anemia) with
> myelodysplastic marrow since 2.5 yrs of age:
>
> -       BM always consistent with normo or hypercellular, increased
> megakaryocytes including hypolobated forms.
>
> -       He was on steroids from 12/2003 to 4/2007 with no obvious benefit
>
> -       WES – Heterozygous FANCM mutation (inherited from father) and 2
> mutations in FANCA (inherited from mother). None of the mutations have been
> described in the literature (variant of unknown significance). (Targeted
> exome sequencing performed on the proband’s and parental blood samples
> identified three missense heterozygous variants of uncertain clinical
> significance (VOUS) in autosomal recessive disease: 1). FANCM (c.5708A >G,
> p.E1903G) (Chr14, 45665742), 2). FANCA (c.377C >T; p.T126M) (Chr16,
> 89877386) and 3). FANCA (c.1928C >G; p.P643R) (Chr16, 89839765). In-silico
> analysis predictions on amino acid changes that effects protein function
> were consistent for FANCM (c.3852C >A) and FANCA (c.1928C >G) as
> deleterious and damaging. Whereas predictions for FANCA (c.377C >T) were
> predicted as neutral & tolerated by Provean and SIFT.)
>
> -       Fanconi (DEB stimulated chromosomal breakage) negative x 3
>
> -       Telomere length study was normal
>
> -       PNH (CD59)- negative
>
> -       Soluble vitamins and trypsinogen to R/O Schwachman-Diamond –
> normal
>
> -       AFP to R/O ataxia-telangiectasia – normal
>
> -       Skeletal survey – normal
>
>
>
> INFECTIONS:
>
> -       Fungemia (Candida) while on steroids (11/2004)
>
> -       Recurrent perforated otitis media in 2006 during chronic steroid
> treatment
>
> -       Skin abscess (1/2011)- grew MSSA
>
> -       MSSA bacteremia in 2013
>
> -       12/2014: MRSA sepsis
>
> -       On co-trimoxazole prophylaxis - no infections since Dec 2014.
>
>
>
> OTHER:
>
> -       Failure to thrive
>
> -       Developmental delay – no dysmorphism, no café au lait
>
> -       Mitral valve insufficiency diagnosed at 3 yrs of age –has been on
> Enalapril and Digoxin
>
> -       Vitreous hemorrhage in 2009, s/p L eye evacuation
>
> -       1 to 6/2015: Subsequent weight loss, increased exercise
> intolerance and fatigue due to progressively worsening mitral regurg.
>
>
>
>
> Immunology work-up (2015):
>
>             Immunoglobulins G normal (921) or elevated (up to 1500), IgA
> slightly low (26), M low (20)
>
>             Protective titers to pneumococcus, tetanus, Hib, MMRV, HepB
>
>             Low CD3 (355), CD4 (150), CD8 (171), B-cell: low (25), NK
> cell; normal (188)
>
>             Mitogen and antigen proliferation: pending
>
>
>
> Family History: negative for any known blood or genetic disorders. Parents
> are not consaguinous. Mother is Puerto-Rican, father is half African
> American, half Puerto-Rican.
>
>
>
>
> In addition to team's question regarding lymphopenia and concerns about
> immunosuppression, I wanted to ask your opinion about FANCA and FANCM
> mutations. Could this case still be a Fanconi anemia case? Does negative
> DEB stimulation always rule out Fanconi? Is there any other test you would
> recommend?
>
>
> Thanks for reading and your input,
>
>
> Yesim
>
>
> Yesim Yilmaz Demirdag, MD
>
> Columbia University Medical Center
>
> phone: (212) 305 2300
>
>
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-- 
Jean Jacques De Bruycker

5429 Monkland
Montréal, QC
H4A 1C5

129 Rice Street  Appt. D
Edmundston, NB
E3V 1T5

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