[CIS PIDD] [cis-pidd] Thoughts about MAP3K14

Wed Apr 12 13:45:29 EDT 2017

HI Everyone,

I wanted to ask for thoughts about a patient who we found to have a heterozygous variant in MAP3K14 and I would like hear thoughts on exploring the relevance of this variant.

The patient is a 4y/o female who was

hospitalized with fever, massive hepatosplenomegally, cytopenias in July 2016.  At the time she had EBV positive PCR.  It was during the hospitalization that whole exome was obtained and the variant found.

Prior to the above hospitalization, she had been seen in immunologydue to difficulty with recurrent sinopulmonary infections and had 2 hospitalizations for fever (one with abdominal adenopathy and the other with norovirus).  At that time, her immunology labs were notable for mild-moderate T cell lymphopenia, elevated IgG but other immunoglobulins normal, protective tetanus responses and a poor pneumococcal response that responded well to pneumovax stimulation.

This winter she has continued to have difficulty with recurrent sinus infections.

Her most current labs are somewhat better although her CD4 count is still a bit low for age and there are fewer naïve T cells than I would expect.  She also has protective tetanus and pneumococcal titers.

Component
Latest Ref Rng & Units

7/14/2016

10/11/2016

12/13/2016

4/6/2017

CD3+
43 - 76 %

78.9 (H)

65.5

67.0

66.3

CD3+ Absolute
900 - 4500 cells/µl

1120

1205

1072

1008

CD3+/CD4+
23 - 48 %

42.1

26.2

32.0

28.8

CD3+/CD4+ Absolute
500 - 2400 cells/µl

598

482 (L)

512

438 (L)

CD3+/CD8+
14 - 33 %

33.0

35.4 (H)

32.2

33.7 (H)

CD3+/CD8+ Absolute
300 - 1600 cells/µl

469

651

515

512

CD19+
14 - 44 %

10.3 (L)

18.0

19.6

15.1

CD19+ Absolute
200 - 2100 cells/µl

146 (L)

331

314

230

CD20+
3.1 - 21.5 %

10.3

17.7

17.8

14.5

CD20+ Absolute
0 - 479 cells/µl

146

326

285

220

CD3-/CD16(B73.1)+ and/or CD56+
4 - 23 %

9.4

10.8

11.4

17.6

CD3-/16(B73.1)+ and/or 56+ Abs
100 - 1000 cells/µl

133

199

182

268

CD4+/CD45RA+
12.5 - 42.2 %

5.9 (L)

5.9 (L)

7.6 (L)

7.7 (L)

CD4+/CD45RA+ Absolute
41 - 1121 cells/µl

84

109

122

117

CD4+/CD45R0+
10.1 - 27.9 %

36.6 (H)

17.0

23.0

19.4

CD4+/CD45R0+ Absolute
153 - 582 cells/µl

520

313

368

295

CD4+/CD8+ Ratio
0.9 - 2.9

1.3

0.7 (L)

1.0

0.9

Immunoglobulin G
539 - 1597 mg/dL

1340 (H)

1350

Immunoglobulin A
48 - 336 mg/dL

187

197

Immunoglobulin M
50 - 194 mg/dL

115

80

Thanks for any suggestions!

Jen

Jennifer Heimall, MD
Allergy/Immunology Attending Physician
Medical Director Day Medicine
Assistant Professor of Clinical Pediatrics
Perelman School of Medicine at University of Pennsylvania

The Children's Hospital of Philadelphia
3401 Civic Center Blvd
Philadelphia, PA 19104
215-590-2549[X] (p)
215-590-6849[X] (f)
________________________________
From: cis-pidd at lyris.dundee.net <cis-pidd at lyris.dundee.net> on behalf of CIS-PIDD <cis-pidd at lists.clinimmsoc.org>
Sent: Wednesday, April 12, 2017 11:35 AM
To: CIS-PIDD
Subject: [cis-pidd] stopping Adagen prior to transplant

Colleagues,
I need a recommendation on the timing of stopping Adagen prior a fully matched MUD in a 19 yo ADA deficiency SCID who was diagnosed at about 15 months of age when he presented with multi system organ failure following varicella vaccination. Except for an episode of cryptococcal meningitis at about age 12 he had done relatively well on Adagen, IG, TMP/SMX and, since the meningitis, fluconazole until 1.5 years ago when he presented with fever, weight loss and chronic diarrhea.

He was found to have a very significant peripheral and bone marrow NK lymphocytosis and was thought to have an indolent NK leukemia. He was treated with supportive care but continued to deteriorate and developed pancytopenia. Colonoscopy and repeat bone marrow nine months ago showed MAI. He has been treated with a multidrug regimen for the MAI and GI symptoms have resolved, NK lymphocytosis has improved but the pancytopenia has not. He is transfusion dependent and has shown no signs of marrow recovery despite adequate nutrition.

A well matched donor has been identified and the plan is to myeloablate with busulfan and cyclophosphamide. The transplanters are considering ATG as well. The question is when to stop Adagen?

Thanks,
Richard
--
Richard L. Wasserman, MD, PhD
Allergy Partners of North Texas
7777 Forest Lane, Suite B-332
Dallas, Texas 75230
Office (972) 566-7788[X]
Fax (972) 566-8837[X]
Cell (214) 697-7211[X]

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