[CIS PIDD] [cis-pidd] ?SCID with severe neutropenia

[CIS-PIDD]

Jen
We did the comprehensive SCID panel from Genedx, they do a CGH and next gen sequencing
Nick


Nicholas Hartog, MD
Allergy and Clinical Immunology
Clinical Assistant Professor – Michigan State University College of Human Medicine


> On Dec 9, 2017, at 7:43 AM, CIS-PIDD <cis-pidd at lists.clinimmsoc.org> wrote:
> 
> Hi Nick
> Was testing done with an array to see if there was a complementary deletion?
> Given the neutropenia and t-b-nk+ phenotype I would also consider moesin defects although that is x-linked so less likely in a girl. 
> Jen Heimall
> 
> Sent from my iPhone
> 
> On Dec 8, 2017, at 5:28 PM, CIS-PIDD <cis-pidd at lists.clinimmsoc.org> wrote:
> 
>> I wanted to reach out about a patient who came to us because of positive newborn screen and an original TREC level of 3.  She is now  1 month old with presumed SCID.
>>  
>> Flow showed (repeated and confirmed results):
>> CD3-80
>> CD4-29
>> CD8-19
>> CD19-75
>> CD16/56-460
>> CD45/4/RA-4 (15%)
>> CD45/4/R0-22 (77%)
>> CD45/8/RA-11 (57%)
>> CD45/8/R0-6 (31%)
>> 56% of CD4+ cells and 9% of CD8+ are positive for HLA-DR.
>>  
>> ALC has remained low (500-700 depending on day) and absolute neutrophil count is zero, she has not responded to G-CSF (2 different occasions).  She also has a very faint erythema and scaling (honestly not that bad at all and nothing like omenn I have seen, but also definitely not normal skin).  IgE is <2 and eosinophils have been normal.  No lymphadenopathy and no hepatosplenomegaly.  She had spectratyping that came and showed oligoclonal/non-Gaussian distribution, polyclonal expression in 3 families of TCR V beta repertoires.   Proliferation was normal to PHA for % of CD45-53.5% (normal>49.9) and CD3-83.1 (normal>58.5), not enough cells for PWM.
>>  
>> Genetic testing showed a heterozygous variant of unknown significance in PRKDC c.5446C>T (p.R1816C).  Not present in ExAC and predicted to be deleterious, but heterozygous.  Also tested and no pathogenic variants in ADA, AK2, ATM, CD3D, CD3E, CD3Z, CORO1A, DCLRE1C, DOCK8, FOXN1, IL2RG, IL7R, JAK3, LIG4, NHEJ1, ORAI1, PNP, PTPRC, PRKDC, RAC2, RAG1, RAG2, RMRP, STIM1, TBX1, ZAP70.
>>  
>> Skin biopsy
>> Examination of the biopsy reveals orthokeratosis and a relatively unremarkable epidermis overlying a mildly dense superficial and mid dermal periadnexal and interstitial infiltrate composed of lymphocytes, histiocytes, scattered neutrophils and rare eosinophils. To better evaluate the infiltrate, immunohistochemical stains were performed. The infiltrate is composed predominantly of CD20 positive B cells. Very rare scattered CD3 positive T-cells are present, with retention of CD5 and CD7 expression. The CD4 to CD8 ratio is within normal limits; however, very few T-cells are present. C25 and CD30 are negative. The Ki-67 proliferative index is approximately 30% within the infiltrate. Neither fungal microorganisms nor basement membrane changes are seen with interpretation of a PAS histochemical stain.
>>  
>> Overall, the findings are relatively mild and not entirely specific. Given the composition of the infiltrate, we considered the possibility of a dermal hypersensitivity reaction, such as urticaria, a drug eruption, or an arthropod bite eruption; however, this does not seem to fit the clinical impression. We also considered the possibility of a viral exanthem. The findings present in the current biopsy do not show an increased population of activated T-cells, as can be seen in Omenn syndrome. These findings are best interpreted in correlation with physical findings, clinical history, and the results of additional studies, as clinically indicated
>> 
>> We just got the results on genetic testing back today and are attempting to figure out the significance (if any) of the PRKDC variant.  Obviously only 1 potentially deleterious variant was identified in an AR condition.
>> 
>> Thank you everyone for any help/assistance with this difficult case.  Have a great weekend
>> Nick
>> 
>> -- 
>> 
>> 
>> Nicholas Hartog, MD
>> 
>> Allergy/Immunology
>> 
>> Assistant Professor
>> 
>> Michigan State University College of Human Medicine
>> 
>> 
>> C: 608-347-1856
>> 
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