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

[CIS-PIDD]

Dr. Chong:

Two thoughts --

#  The chicken and egg question -- might the T/B/NK lymphopenia and specific IgG loss be a product of the infant's GI disease?  Is there a relation between his numbers and when his GI disease flares, versus when it is in more proper control.  How often is the boy on steroids -- this would more than certainly cause lymphopenia.

#  MTM1 is within spitting distance of IRAK1 (first cousin of IRAK4, of TLR4/MyD88 fame).  I don't know if there is a defined phenotype to an IRAK1 mutation.  (If there is, please correct me).  But, for what it's worth, it looks like MTM1 and IRAK1 are within the end of the q arm of the X chromosome (Xq28).  If there's an issue with one, there might be an issue with the other.  'Might explain your abnormal TLR assay.

Good luck.

  - K

Karl O. A. Yu, M.D., Ph.D., F.A.A.P.
Instructor of Pediatrics (Pediatric Infectious Diseases)
University of Chicago - Comer Children's Hospital
5841 S Maryland Ave, MC 6054, Chicago IL 60637
Pager:  773-702-6800   x1744
Fax:  773-702-1196
Lab phone (Bubeck Wardenburg laboratory): 773-834-6976


________________________________________
From: CIS-PIDD [cis-pidd at lists.clinimmsoc.org]
Sent: Monday, July 18, 2016 12:43 PM
To: CIS-PIDD
Subject: [cis-pidd] Seeking advice on early and severe IBD

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<http://www.omim.org/entry/605257>, BTK<http://www.omim.org/entry/300300>, CD40LG<http://www.omim.org/entry/300386>, CYBA<http://www.omim.org/entry/608508>, CYBB<http://www.omim.org/entry/300481>, DCLRE1C<http://www.omim.org/entry/605988>, FOXP3<http://www.omim.org/entry/300292>, HPS1<http://www.omim.org/entry/604982>, HPS4<http://www.omim.org/entry/606682>, HPS6<http://www.omim.org/entry/607522>, ICOS<http://www.omim.org/entry/604558>, IL10RA<http://www.omim.org/entry/146933>, IL2RA<http://www.omim.org/entry/147730>, LRBA<http://www.omim.org/entry/606453>, MEFV<http://www.omim.org/entry/608107>, MVK<http://www.omim.org/entry/251170>, NCF2<http://www.omim.org/entry/608515>, NCF4<http://www.omim.org/entry/601488>, PTEN<http://www.omim.org/entry/601728>, RET<http://www.omim.org/entry/164761>, SH2D1A<http://www.omim.org/entry/300490>, SLC37A4<http://www.omim.org/entry/602671>, STXBP2<http://www.omim.org/entry/601717>, TTC37<http://www.omim.org/entry/614589>, WAS<http://www.omim.org/entry/300392>, XIAP<http://www.omim.org/entry/300079>

            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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