[CIS PIDD] [cis-pidd] XLP on screening

Wed Oct 18 18:34:03 EDT 2017

We have seen a number of these....ours seems to be in adults.  We just did a functional assay for XIAP in an adult with Crohn(outside patient) and he was XIAP deficient.  He was also nearly 30 but apparently EBV naïve.  We have another with CVID that may be EBV naïve.  In the former there was no protein and no function.  In the later protein was present and there was detectable function but it was not normal (about 1/2 of the LLN)

I don't know the answer to this.  In the case above our patient was on Rituxan for other reasons and thus we feel we can keep him on that and IVIG and keep him from getting EBV.  In the other case he has resistant Crohns so they may be doing a transplant anyway.

Regardless, this is a young kid with a stop codon...so this is likely to be XLP2.  Do you just wait for EBV?  Do you give IVIG?  Do you give rituxan to prevent EBV?

No one knows the answer.  We have chosen to treat the adults with Rituxan and IVIG...and are not doing a transplant since they are doing well

Not to advertise our lab since I know Cinn also does XIAP expression, but we do XIAP protein expression and a functional assay with MDP.

Best

James

James Verbsky MD/PhD
Associate Professor of Pediatrics and Microbiology and Molecular Genetics
Medical College of Wisconsin
Milwaukee, WI  53226

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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, October 18, 2017 5:14 PM
To: CIS-PIDD
Subject: Re: [cis-pidd] XLP on screening

Burkitt like lymphoma and SH2D1A mutation make sense for transplant, but an asymptomatic child with an unknown XIAP variant doesn't. Even if it was a known pathologic mutation, I don't think we would recommend transplant yet. You could look for XIAP protein expression by flow and if normal, unlikely this is pathologic. This is a bit hard to comprehend or rather explain, but we need to stick to the science - these assays should not be used as screening tools.

Ashish
Ashish Kumar, MD, PhD
Associate Professor
Director, Pediatric Hematology-oncology fellowship program
Director, Langerhans cell histiocytosis center
Cincinnati Children's Hospital Medical Center

On Oct 18, 2017, at 4:53 PM, CIS-PIDD <cis-pidd at lists.clinimmsoc.org<mailto:cis-pidd at lists.clinimmsoc.org>> wrote:

We just had a scarily similar case…

Patient had WES for developmental delay.  He came into the seen when the (in his case SH2D1A) mutation was found.  Upon arrival- he had adenopathy and it turned out to be a Burkitts like lymphoma.

I think they can do bad things in unpredictable ways and a three year old is more resilient for a transplant than an older kiddo/adult.

Kate
Sullivan, Kathleen 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
sullivank at email.chop.edu<mailto:sullivank at email.chop.edu>

On Oct 18, 2017, at 4:47 PM, CIS-PIDD <cis-pidd at lists.clinimmsoc.org<mailto:cis-pidd at lists.clinimmsoc.org>> wrote:

Dear All:

I was consulted on the following case and would appreciate your input:

A 3 year old male, with a family history of Adams-Olivier syndrome, underwent screening when he was a newborn by whole-genome sequencing in what appears to be an accredited diagnostic laboratory in the U.S. (I do not have further details... I think he was screened because of the potential neuro-developmental delays associated with this disorder; he did not have any of the associated malformations).

While he did not have any mutations in genes associated with the targeted syndrome, he was found to have a variant in XIAP (NM_001167; c.340C>T; p.Gln114*). This is obviously predicted to be deleterious.

He is asymptomatic, including no GI symptoms.
He has been treated with IVIG, as prophylaxis against EBV. He has no hypo/dys-gammaglobulinemia (prior to starting IVIG at around 2 years of age).

Given the broad presentations of XIAP deficiency, what recommendations would you make? Specifically, would you recommend going to HSCT ASAP?

Thanks,
Don

Donald C. Vinh, MD, FRCP(C)
Director, Infectious Disease Susceptibility Program
Lilian Wilkins Associate Professor, FRQS Clinician-Scientist
Dept of Medicine (Division of Infectious Diseases; Division of Allergy & Clinical Immunology)
Dept of Medical Microbiology; Dept of Human Genetics

McGill University Health Centre - Research Institute
1001 Decarie Blvd; Block E; Rm EM3-3230 (Mail Drop: EM3-3211)
Montreal, Quebec,  Canada H4A 3J1

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