[CIS PIDD] [cis-pidd] 17 mo M with autoimmune cytopenias, hypotonia, 3rd nerve palsy

Fri Jun 19 15:58:55 EDT 2015

You could do an Apoptosis assay?

Consider: 
STAT3 GOF
http://www.ncbi.nlm.nih.gov/pubmed/?term=Early-onset+lymphoproliferation+and+autoimmunity+caused+by+germline+STAT3+gain-of-function+mutations <http://www.ncbi.nlm.nih.gov/pubmed/?term=Early-onset+lymphoproliferation+and+autoimmunity+caused+by+germline+STAT3+gain-of-function+mutations>

LRBA
http://www.ncbi.nlm.nih.gov/pubmed/25931386 <http://www.ncbi.nlm.nih.gov/pubmed/25931386>

Elena

> On Jun 19, 2015, at 11:48, Jonathan Tam <kiditamae at gmail.com> wrote:
> 
> We here at CHLA have a case of a 17 month old M with autoimmune cytopenias
> (thrombocytopenia, hemolytic anemia and neutropenia), hypotonia and new 3rd
> nerve palsy with no focal findings on MRI.
> 
> He was increase in double negative T cells (CD3+ CD4-CD8-, TCR a/b 5.1%),
> but no palpable lymphadenopathy (only LAD on CT) and normal looking nodes
> on biopsy.
> 
> 
> 
> Any input would be appreciated.
> 
> Thoughts on Rituxan for for this patient?
> Further diagnositic studies?
> 
> 
> 
> 
> 
> 
> 
> *Patient Summary*:
> 
> 
> 
> Patient is a now 13-month-old boy with a history of developmental
> delay, hypotonia and febrile seizure who was first seen 12/2014 with
> thrombocytopenia that was responsive to IVIG.   He was then hospitalized
> 4/26-4/28/15 for fever, hypoxemia found to be +metapneumovirus.  He
> represented on 4/29 to an outside hospital due to persistent fever,
> possible febrile seizure, and respiratory distress.  At the OSH he was
> treated for PNA diagnosed on CXR with vancomycin and ceftriaxone x14 days.
> He was noted to have thrombocytopenia and received 6 g IVIG on 5/21/15.
> Developed new dysconjugate gaze with L lid half closed, evaluated by peds
> neuro with *MRI brain and orbits reported negative *except for right
> sphenoid and ethmoid sinus disease.  He was subsequently transferred back
> to our care.
> 
> 
> 
> Repeat MRI/MRA/MRV did not detect any focal lesions in the brain.  CT of
> the chest abdomen and pelvis did note hilar, mediastinum, retroperitoneum,
> and groin adenopathy.  Additionally in the chest there was patchy
> “bilateral lung opacities both upper and lower lungs that may be
> infectious/inflammatory, but areas of atelectasis/scarring not excluded”.
> 
> 
> 
> LN biopsy on a node from the groin did not show any significant
> abnormalities (no cancer, not consistent with ALPS).  Bone marrow was
> similarly underwhelming.
> 
> 
> 
> Ophtho and neurology calling the new ptosis Miller-Fisher variant
> Guillain-Barre syndrome.  Neuronal ab screen (Hu) was positive, but western
> blot was negative.
> 
> 
> 
> 
> 
> FH:
> 
> --No consanguinty.  No history of recurrent infections.
> 
> --The patient's mother is of Filipino and Mexican descent. The patient's
> father is of Mexican descent.
> 
> --Maternal uncle, paternal uncle, and grandmother with asthma.  Mom with
> atopic dermatitis.  Paternal uncle with allergic rhinitis.  No family
> history of thrombocytopenia
> 
> 
> 
> SH: Recently moved to LA from New Mexico.  2 dogs at home.  No smokers at
> home.  Lives with mom, dad, paternal uncle, and paternal grandparents.
> 
> 
> 
> Birth history: Born full term via NSVD.  No complications. Birth weight 5
> lbs 6 oz.  No NICU stay. Born in New Mexico (no newborn screen)
> 
> 
> 
> Developmental history:  Crawls (started at age 12 months), Cruises (started
> at 15 months), Says mama and dada (started at 10 months), Reaches for
> objects
> 
> 
> 
> *Labs/Imaging*:
> 
> 
> 
> *CD3+                                 17.5 %*
> 
> *Abs CD3+                        296 Cells/uL*
> 
> *CD3+CD4+                       9.0 %*
> 
> *Abs CD4+                        152 Cells/uL*
> 
> *CD3+CD8+                       6.3 %*
> 
> *Abs CD8+                         106 Cells/uL*
> 
> 
> 
> *CD3+ CD4-CD8-, TCR a/b    5.1%*
> 
> 
> 
> *CD3/4+ CD45RA+           2%*
> 
> *CD31+CD45RA+            <1%*
> 
> 
> 
> TREC sent to Viracor >950 (normal >801)
> 
> 
> 
> *CD25+CD127dim+         4%*
> 
> 
> 
> CD3-CD16+CD56+         20.0 %
> 
> Abd NK                             338 Cells/uL
> 
> CD3+HLA DR+                 5 %
> 
> CD19+                                60.3 %
> 
> Abs CD19+                       1,021 Cells/uL
> 
> IgD-CD27+CD19+           10%
> 
> 
> 
> NK function normal
> 
> 
> 
> IgG 1,760 mg/dL  (one week after IVIg for thrombocytopenia)
> 
> IgM 387 mg/dL
> IgA 128 mg/dL
> 
> 
> 
> C3            88 mg/dL
> C4            22 mg/dL
> CH50       238 Unit
> 
> 
> 
> 
> 
> 12/23/14
> 
> 12/27/14
> 
> 3/11/15
> 
> 4/24/15
> 
> 5/28/15
> 
> WBC
> 
> 6.22 K/uL
> 
> 7.19 K/uL
> 
> 3.43 K/uL
> 
> 5.45 K/uL
> 
> *3.60 K/uL*
> 
> ANC
> 
> 2150
> 
> 2000
> 
> 1960
> 
> 600
> 
> *0*
> 
> ALC
> 
> 2740
> 
> 3390
> 
> 1280
> 
> 3160
> 
> 1690
> 
> RBC
> 
> 3.52 M/uL
> 
> 4.10 M/uL
> 
> 3.20 M/uL
> 
> 3.53 M/uL
> 
> 2.64 M/uL
> 
> HGB
> 
> 9.0 g/dL
> 
> 10.9 g/dL
> 
> 8.3 g/dL
> 
> 9.6 g/dL
> 
> *7.8 g/dL*
> 
> HCT
> 
> 27.4 %
> 
> 32.3 %
> 
> 26.6 %
> 
> 29.3 %
> 
> 24.7 %
> 
> MCV
> 
> 77.8 fL
> 
> 78.8 fL
> 
> 83.1 fL
> 
> 83.0 fL
> 
> 93.6 fL
> 
> MCH
> 
> 25.6 pg
> 
> 26.6 pg
> 
> 25.9 pg
> 
> 27.2 pg
> 
> 29.5 pg
> 
> MCHC
> 
> 32.8 %
> 
> 33.7 %
> 
> 31.2 %
> 
> 32.8 %
> 
> 31.6 %
> 
> PLT
> 
> *13 K/uL*
> 
> 218 K/uL
> 
> *41 K/uL*
> 
> 107 K/uL
> 
> *9 K/uL*
> 
> RDW
> 
> 14.8 %
> 
> 14.9 %
> 
> H 15.6 %
> 
> H 16.7 %
> 
> H 18.2 %
> 
> 
> 
> O+, *DAT+ and warm antibody positive.*
> 
> 
> 
> Neuronal (Hu) ab screen positive, but western blot *negative*
> 
> 
> 
> HIV, EBV, CMV HSV PCR negative
> 
> 
> 
> Free T4     0.72 ng/dL
> TSH            1.81 uIU/mL
> Thyroid Stim Immunoglobulin    * <89 % baseline
> Thyroglobulin ab    * <244 I.U./mL (Negative)
> TPO    * <33.4 I.U./mL (Negative)
> 
> 
> LKM ab <20
> Smooth muscle ab 29 (normal <20)
> 
> LN biopsy - Both H\T\E stained sections demonstrate benign lymph nodes
> with mild follicular hyperplasia and mild paracortical expansion.
> Germinal centers are well formed with a crisp mantle zone. The
> paracortex is composed of a heterogeneous population of small
> lymphocytes, immunoblasts, plasma cells and with mild vascular
> proliferation. There is focal sinus histiocytosis (A2)
> 
> 
> Abd US:  Nonspecific coarsened echotexture within the liver, which can be
> seen in infiltrative processes such as steatosis. No discrete liver lesion
> or evidence of biliary duct dilatation.
> 
> 
> 
> MRI/MRA/MRV Brain/Orbits:
> 
> --No evidence of acute infarct, hemorrhage, hydrocephalus, or mass.
> 
> --No signal abnormality or abnormal enhancement within the orbits.
> 
> --Normal course and caliber the visualized portions of the circle of Willis.
> 
> --No evidence of occlusion or high-grade stenosis of the major dural venous
> sinuses.
> 
> 
> 
> CT Chest/Abd/Pelvis:
> 
> 1. Patchy bilateral lung opacities both upper and lower lungs that maybe
> infectious/inflammatory, but areas of atelectasis/scarring not excluded.
> Greatest area is at right base where it seems more consolidated.
> 
> 
> 2. Right hilar, mediastinum, retroperitoneum, groin adenopathy of which
> some are partially calcified at the right groin along with
> 
> hepatosplenomegaly. Would wonder about granulomatous disease whether TB or
> cocci since calcified nodes are less typical for histiocytosis
> 
> or cat scratch. Otherwise could relate to other
> rheumatologic/infectious/inflammatory process. Further down the
> differential would be leukemia/lymphoma (not typical for neuroblastoma).
> 
> 
> 
> Swallow study normal.
> 
> 
> 
> ---------------------------------------------------
> 
> Jonathan Tam, MD
> 
> Assistant Professor of Pediatrics
> 
> Division of Clinical Immunology & Allergy
> 
> Children’s Hospital Los Angeles
> 
> 4650 Sunset Blvd, MS#75
> 
> Los Angeles, CA 90027
> 
> jstam at chla.usc.edu
> 
> Phone: 323.361.2501
> 
> Fax: 323.361.1191
> 
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