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

[Yeşim Yılmaz Demirdağ]

Thanks Dr. De Bruycker,
His monocyte counts range between 500 and 1200, he does not have
pulmonary hypertension and any evidence of PAP.
Yesim

On 7/22/15, Jean Jacques De Bruycker <jjdebruycker at gmail.com> wrote:
> 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
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>
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