[CIS PIDD] [cis-pidd] Neutropenia and low interferon gamma production

Fri Sep 5 08:17:34 EDT 2014

Thanks for the reply Dylan.  The only other systemic manifestation was early onset diarrhea that has now resolved.  I was considering Shwachman-Diamond syndrome until his GI symptoms resolved.  

Lynn A. Wiens, MD

Cell: 918-550-1200

http://tulsaallergynews.com <http://tulsaallergynews.com> 

From: Dylan Mordaunt [mailto:d.a.mordaunt at gmail.com] 
Sent: Thursday, September 04, 2014 19:02
To: CIS-PIDD
Subject: Re: [cis-pidd] Neutropenia and low interferon gamma production

Dear Lynn,

Were there any other features such as developmental delay, liver dysfunction or hypoglycemia?

Although relatively uncommon, many of the metabolic neutropenias can be solved with urine organic and amino acids as well as urine purine and pyrimidine profiling- both relatively inexpensive tests. Barth syndrome and GSD1b are probably the more common metabolic neutropenias we encounter in the metabolic clinic, although GSD1b requiring GCSF would be having frequent low BSLs.

Interestingly, there are no disorders annotated with 'abnormalities of interferon secretion' (HPO code HP:0011116) in the Mendelian Inheritance in Man database (omim.org), presumably because this is predominantly edited by geneticists rather than immunologists. It may also be that you are observing a phenomenon in a known disorder, but which has not previously been reported.

There are a few broad-based genetic testing options if you do not have a short differential. There are two 'neutropenia' NGS panels I am aware of: http://www.ncbi.nlm.nih.gov/gtr/tests/512562/ and https://www.preventiongenetics.com/clinical-dna-testing/test/severe-congenital-neutropenia-sanger-sequencing-panel/476/.

These panels are limited in terms of the number of genes but coverage (of the individual genes) is likely to be good. Another option would be to create a 'custom' panel with a lab like Fulgent (fulgent-therapeutics.com/test/), cost is USD $1495. They perform a massive panel/exome but perform a 'virtual panel' by only filtering for variants in the gene of interest. You can add up to 20 genes with Fulgent (I think GeneDx have a similar service), reflex to del/dup for another $500. You would just need to be aware that gene coverage can be a limitation depending on the genes of interest but if you found a pathogenic variant in a recessive gene with poor coverage, could subsequently Sanger sequence the remaining gene.

Kind regards,

Dylan

Dylan Mordaunt

Clinical and Metabolic Genetics Fellow

South Australian Clinical Genetics Service

Mobile: + 61 468 516 283
Email: d.a.mordaunt at gmail.com

On 4 September 2014 23:30, Wiens, Lynn A MD <lawiens at saintfrancis.com> wrote:

I am taking care of a 2 yo male with idiopathic neutropenia doing well on Neupogen.  As part of his work-up, I obtained T-cell function and PHA did upregulate CD 69 but there was no interferon gamma production.  In vitro proliferation to tetanus toxoid, viral mixture, candida was low.  Response to PWM; staph superantigen was normal.  

My question is what additional genetic testing is indicated in a boy doing well with neupogen; no additional infections since starting.  

Lynn A. Wiens, MD

Warren Clinic

6160 South Yale Avenue  Tulsa, OK 74136

Specializing in the care of Allergy, Asthma, Sinus disease, and Chronic Infections

http://tulsaallergynews.com <http://tulsaallergynews.com> 

Office: 918-495-2636

Cell: 918-550-1200

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