[CIS PIDD] [cis-pidd] SCID genetic diagnosis?

Tue Aug 23 13:25:30 EDT 2016

Thanks Mike,
Unfortunately, the one sibling is not a match and there are no fully matched donors.

Niraj
________________________________________
From: CIS-PIDD <cis-pidd at lists.clinimmsoc.org>
Sent: Tuesday, August 23, 2016 10:49 AM
To: CIS-PIDD
Subject: Re: [cis-pidd] SCID genetic diagnosis?

*CAUTION: External Email*

Hi Niraj,

You could parse the areas of LOH in UCSC genome browser for potential causative genes.

Does she have any healthy matched sibs or fully matched donors?

Best,
Mike

Sent from my iPhone

> On Aug 23, 2016, at 10:42 AM, CIS-PIDD <cis-pidd at lists.clinimmsoc.org> wrote:
>
> Dear All,
>
> I need help with a diagnostic dilemma.
>
>
> An 8 month old female born 36 weeks to consanguineous parents. Pregnancy was complicated by hydrops and cardiac ventricular hypertrophy. She has a history of pulmonary valve stenosis, dysmorphic facies, failure to thrive and chronic diarrhea.  At 6.5 months of age, she presented in respiratory failure, bronchoscopy showed Pneumocystis jirovecii, rhinovirus, parainfluenza virus. She completed treatment with IV Bactrim and steroids.  She had severe CD3T cell lymphopenia, agammaglobulinemia, and family history of sibling who died of pneumonia at 6 months of age, and the working diagnosis was SCID.  An extensive infectious disease evaluation (CMV, rotavirus, adenovirus, enterovirus, others) was negative.
>
>
>
> Other past medical history included anemia at birth requiring 2 blood transfusions, cardiomyopathy, hepatomegaly.  Amniocentesis showed normal chromosomes. Microarray showed multiple extensive regions of homozygosity consistent with consanguinity.
>
>
>
> LAB EVALUATION AT PRESENTATION
>
> WBC 4,000
>
> ANC 2,700
>
> ALC 360
>
> CD3T  102
>
> CD4T 63
>
> CD8T 3
>
> CD4/CD8 21.0
> CD56/16 72
>
> CD19 179
>
> IgG <170
>
> IgA <2
>
> IgM <20
>
> TREC  < 5 copies
>
> T cell stimulation: attempted twice, sample insufficient
>
> Genetic Testing: Comprehensive SCID panel (46 genes by sequencing only; del/dup not done) to Baylor was negative (ADA, AK2, AP3B1, CASP8, CD3D, CD3E, CD3G, CD8A, CHD7, CIITA, CORO1A, DCLRE1C, DOCK8, FOXN1, FOXP3, IKZF1, IL2RG, IL7R, ITK, JAK3, LCK, LIG4, LYST, NHEJ1, ORAI1, PNP, PRF1, PRKDC, PTPRC, RAG1, RAG2, RFX5, RFXANK, RFXAP, RMRP, SH2D1A, STAT5B, STIM1, STX11, STXBP2, TAP1, TBX1, TTC7A, UNC13D, XIAP, ZAP70)
>
> HIV PCR - negative
>
> ADA and PNP levels on RBC normal, but done 1 week after blood transfusion
>
>
>
> INTERVAL HISTORY
>
> At 7.5 months of age, the WBC steadily declined from 7, 100 to 1, 500, and hemoglobin declined from 13.3 to 8.0.  Platelets are normal
>
> ANC 1,100
>
> ALC 300
>
> CD3T 171
>
> CD4T 126
>
> CD8T 8
>
> CD4/CD8 15.8
>
> CD19B 48
>
> CD56/16 67
>
> Bone marrow biopsy showed cellular marrow with relative erythroid hyperplasia and mildly megaloblastic erythroid maturation.  Normal numbers of megakaryocytes with frequent hypoblate nuclear morphology.  Increased storage iron present, scattered erythroid ring forms seen.
>
>
>
>
>
> Thoughts regarding a genetic diagnosis?
>
> Conditioning regimen for bone marrow transplantation?
>
>
>
> Plan is to send Whole Exome Sequencing.  Any thoughts would be greatly appreciated.
>
>
>
> Thank you,
>
> Niraj
>
>
>
> Niraj Patel, MD, MS
>
> Pediatric Infectious Disease and Immunology
>
> Levine Children's Hospital
>
> Carolinas Medical Center
>
> Charlotte, NC. USA
>
>
>
>
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>
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