[CIS PIDD] [cis-pidd] Febrile 7 month old boy

CIS-PIDD cis-pidd at lists.clinimmsoc.org
Mon Mar 20 19:38:29 EDT 2017


Does the patient has recurrent cold induced urticaria? I don't think we can
fit the NLRP12 genotype with the phenotype. We have a big family in south
Brazil with FCAS phenotype and NLRP12 ( c.910C>T) and all affected members
has cold induced recurrent fever, urticaria, arthritis, abdominal pain and
irritability.

However, with the neurological symptoms presented by your patient and the
mutation found in TREX1 I think its necessary exclude AGS or CL.

you could do Interferon signature (TREX1) and NLFkB degradation (NLRP12 -
IL1B, IL18 and IL6) after 3 hours with ATP and LPS stimullus to see what is
the pathogenic one.



2017-03-20 15:27 GMT-03:00 CIS-PIDD <cis-pidd at lists.clinimmsoc.org>:

> I wanted to follow up on a case I shared last year and see if anyone had
> insight on the recently detected mutation.  Briefly, the infant boy had
> recurrent fevers (hospitalized multiple times with extensive workup),
> anemia of chronic disease, reactive thrombocytosis, and slight hypotonia
> last spring/summer/fall.  His 37-gene fever panel (MNG Laboratories) was
> negative and he didn’t respond much to anakinra.  With the tincture of
> time, his fevers and symptoms have fortunately resolved.   He is now 15
> months and doing much better.
>
> Whole exome sequencing revealed 2 variants of unknown significance (VUS):
>
> *1- NLRP12: Heterozygousc.779C>T(p.T260M) inherited from mother.*
>
> 2-TREX1: Heterozygousc.391T>G (p.F131V) inherited from father
>
>
> Since heterozygous variants in the NLRP12 gene have been reported in
> association with Familial Cold Autoinflammatory Syndrome, I wonder if this
> VUS may be significant?!?!  Again, any recommendations would be much
> appreciated.  Full history with labs and imaging is below.
>
>
> *Cindy Salm Bauer, MD*
>
> Co-Director, Eosinophilic Gastrointestinal Disease Clinic
>
> Co-Director, Immunohematology Clinic
>
> Assistant Professor, Department of Medicine, Mayo Clinic Arizona
>
>
>
> Division of Allergy and Immunology, Department of Pediatric Pulmonology
>
> Phoenix Children's Hospital
>
> 1919 East Thomas Road / Phoenix, AZ  85016 / Tel:  602-933-4063
> <(602)%20933-4063>
>
> cbauer at phoenixchildrens.com
>
> On Mon, Jun 27, 2016 at 5:40 PM, CIS-PIDD <cis-pidd at lists.clinimmsoc.org>
> wrote:
>
>>
>> I thank you in advance as I am struggling with this case and could use
>> your expertise.  This is my first posting and I apologize for it being so
>> very long.
>>
>>
>>
>> Pt is a 7 month old male who presents with nearly constant fevers
>> of unknown origin. He was born full term, uncomplicated pregnancy, only
>> child in the family, and from unconsanguinous parents.  Fevers started
>> at 2-3 weeks of age and have been ongoing with at most a few days to a week
>> between febrile episodes.  There is no discernable pattern; fevers range
>> from 101-103F and do respond to antipyretics.  He has no consistent
>> symptoms with his fever other than being slightly fussy (no vomiting,
>> respiratory symptoms, rash, etc.).  He did have mild truncal hypotonia a
>> few times and, during 1 fever, an episode of upper extremity tremor.  He
>> has crossed percentiles for weight from birth to 4 months, but has been
>> tracking curve appropriately and current weight is 98% of IBW.  He was
>> exclusively breast fed until 2 weeks ago when mom began occasionally
>> supplementing with formula and adding oat to thicken.
>>
>>
>>
>> Fevers have resulted in 3 hospitalizations and extensive workup.  No
>> source or cause has yet been found.
>>
>>
>>
>> *Most Noteable Laboratory Workup (abnormal values in red):*
>>
>>    -
>>
>>    2 weeks of age (inpatient):  CBC/diff normal; CMP with ionized
>>    calcium 1.34 (nl = 1.12-1.32); UA clear; RSV negative; CRP normal at
>>    0.6; negative urine culture, blood culture, stool culture, and LP
>>    -
>>
>>    4 weeks of age (inpatient): CBC/diff normal; negative urine culture,
>>    blood culture; bone scan normal
>>    -
>>
>>    2.5 months:  CBC/diff with platelet count elevated at 548; normal
>>    IgG, IgA, IgM
>>    -
>>
>>    4 months: CMV quantitative normal; lymphocyte subset panel normal;
>>    CMP with calcium 11.1 (nl = 9-11); CBC with platelets 631,000; ESR
>>    elevated at 24, CRP elevated at 6.71
>>    -
>>
>>    5 months:  CRP elevated at 7.4; parvovirus PCR negative; EBV PCR
>>    negative; IgG, IgM, IgE, and IgA normal; IgD <1; nasopharyngeal swab/viral
>>    respiratory panel by PCR—negative for all viruses, Bordetella,
>>    Chlamydophilia and mycoplasma; Quantiferon TB Gold – negative; Fecal
>>    calprotectin elevated at 391; cocci, toxo, parvo, EBV – negative; CMV
>>    PCR- negative; ferritin normal; CH50 normal; ANA negative
>>    -
>>
>>    6 months (inpatient):  CBC with low WBC of 3,600, low Hgb 10.1, low
>>    ANC of 1000, and low ALC of 2.0; lymphocyte subsets with low CD3 1348, CD4
>>    931, CD8 366; CMP normal; CK 134 and 177 (H); LDH 488 (H); ferritin
>>    132 (nl); TSH 6.16 (H); FreeT4 1.24 (nl); C3 77; C4 18; CRP  <0.3;
>>    Sweat chloride - nl; peripheral smear with mild
>>    normochromic/normocytic anemia, reactive appearing lymphocytes, and
>>    borderline thrombocytosis with large platelets
>>    -
>>
>>    6.25 months:  CBC with low Hb of 9.0 and elevated platelets of 833; normal
>>    eye exam
>>    -
>>
>>    6.5 months:  Quantiferon TB Gold – negative; HIV Ab negative; Fecal
>>    Elastase – normal; lymphocyte enumeration normal with no activated T cells
>>    and normal switch memory B cells; elevated IL2R of 1808 (normal 406
>>    to 1100); Bone marrow biopsy normal though anemia of chronic disease
>>    (normal iron sat and ferritin, but low iron saturation) and a reactive
>>    thrombocytosis, without evidence of HLH
>>    -
>>
>>    7 months (this week):  planning to send fever gene panel; GI planning
>>    to EGD and flex/sig
>>
>>
>>
>> *Radiology:*
>>
>>    -
>>
>>    Ultrasound abdomen complete- Normal exam
>>    -
>>
>>    Echocardiogram - normal
>>    -
>>
>>    Brain MRI - normal
>>    -
>>
>>    Bone scan - normal
>>    -
>>
>>    CXR normal
>>    -
>>
>>    PET normal except for slightly increased splenic uptake
>>
>>
>>
>> As above, I am planning to send the fever gene panel this week.  I am not
>> sure on starting any treatment (IL-1 antagonist for example) as I don’t
>> know what I’m treating!
>>
>>
>>
>> Sincerely,
>>
>>
>>
>> *Cindy Salm Bauer, MD*
>>
>> Co-Director, Eosinophilic Gastrointestinal Disease Clinic
>>
>> Division of Allergy and Immunology, Department of Pediatric Pulmonology
>>
>> Phoenix Children's Hospital
>>
>> 1919 East Thomas Road / Phoenix, AZ  85016 / Tel:  602-933-4063
>> <(602)%20933-4063>
>>
>> cbauer at phoenixchildrens.com
>>
>>
>>
>> Clinical Assistant Professor, Department of Child Health,
>>
>> University of Arizona College of Medicine
>>
>>
>>
>>
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-- 

Leonardo Oliveira Mendonça
Médico Especialista em Imunologia Clínica e Alergia, Doenças Autoimunes e
Autoinflamatórias
Médico Especialista em Clínica Médica/Medicina Interna

Leonardo Oliveira Mendonça, MD
Specialist in Clinical Immunology and Allergy, Autoimmune and
Autoinflammatory disorders
Consultant Specialist in Internal Medicine

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