[CIS PIDD] [cis-pidd] Seeking advice on early and severe IBD

[CIS-PIDD]

Dear Hey

I think it’s worth considering the possibility that the known genetic lesion in MTM1 itself is leading to an increased susceptibility to autoimmunity or gut-associated auto-inflammation. MTM1 does appear to be expressed at the mRNA level in immune cells (see public RNA-seq and microarray data on ImmGen.org). Myotubularin-related proteins have been described to affect calcium flux in T cells through phosphoinositide phosphatase activity (Srivastava et al Mol and Cell Bio 2006). Are there regulatory T cells in this child? Do they function normally?

Sincerely,
Manish

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Manish J. Butte, MD PhD 
Assistant Professor of Pediatrics / Immunology & Allergy
Tashia and John Morgridge Faculty Scholar, Child Health Research Institute
Stanford University
mjbutte at stanford.edu
http://tcell.stanford.edu

On July 18, 2016 at 10:44:17 AM, CIS-PIDD (cis-pidd at lists.clinimmsoc.org) wrote:

Dear all,

 

I have a 2 year old male with past medical history of centronuclear myopathy (MTM1 gene mutation) s/p g-tube/nissen/hiatal hernia repair, s/p trach/vent dependent, hydrocephalus s/p VP shunt in 3/23/2014

Diagnosed with severe and refractory Crohns disease around 2 years of age, pancolitis, never true remission despite high dose steroids and high dose remicade. 

He has had had otherwise a benign infectious history with only a few AOM and sinusitis

slightly low T,B, NK cells but normal naïve thymic emigrants, normal quantitative immunoglobulins.  He had normal mitogens

negative tetanus titer despite vaccination

One abnormal TLR assay (while sick and hospitalized)

 

He had genetic testing done through Emory Genetics laboratory

Early Onset Inflammatory Bowel Disease Sequencing Panel

which covers the following genes:

AICDA, BTK, CD40LG, CYBA, CYBB, DCLRE1C, FOXP3, HPS1, HPS4, HPS6, ICOS, IL10RA, IL2RA, LRBA, MEFV, MVK, NCF2, NCF4, PTEN, RET, SH2D1A, SLC37A4, STXBP2, TTC37, WAS, XIAP

 

            And no pathogenic variant was found.

 

Is there something else I am missing?

I would appreciate any thoughts.

 

Thank you very much

 

Hey Chong

 

 

Hey Jin Chong MD PhD  
Assistant Professor of Pediatrics  
Division of Pulmonary Medicine, Allergy & Immunology  
Children's Hospital of Pittsburgh of UPMC  
One Children's Hospital Drive  
4401 Penn Avenue  
Pittsburgh, PA 15224  
tel 412-692-7885  
fax 412-692-8499

 

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