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

Tue Aug 23 16:37:10 EDT 2016

My two cents.  The gene does not make the diagnosis of SCID, leaky SCID or even CID.  If you know the phenotype then you know the path forward.  There are new genes being identified all the time.  Yours may not have a known SCID gene but if the phenotype is SCID or SCID-ish- then you have a path forward and it is transplant.

Kate Sullivan, MD PhD
Wallace Chair
Chief of Allergy Immunology
ARC 1216 CHOP
3615 Civic Center Blvd.
Philadelphia, PA 19104
(p) 215-590-1697
(f) 267-426-0363

On Aug 23, 2016, at 10:41 AM, CIS-PIDD <cis-pidd at lists.clinimmsoc.org<mailto: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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