[CIS PIDD] [cis-pidd] Rib abnormalities in CGD !!!

Fri Jun 30 09:25:25 EDT 2017

Dear all

I would like to update the group on the child with suspected Omenn syndrome
Vs CGD.

Genetic results have not shown any mutation in RAG or SCID-related genes.
No mutation in CGD related genes. But, to my surprise there are 2
homozygous mutations in DOCK8 gene.

1st mutation -  Homozygous mutation   chr9:340251C>T c.1609C>T p.Arg537Trp

2nd mutation - Homozygous mutation  chr9:414922A>C c.3671A>C p.Asp1224Ala

Now I wonder, whether its DOCK8 deficiency !!!

IgE was markedly elevated in this boy. As he is only 4 months old, the
clinical phenotype may not be completely expressed. How do I link rib
abnormalities with DOCK8 deficiency?

Which of the two mutations is the cause of the disease?

Kindly opine

Regards
Sagar

*Dr.Sagar Bhattad*
MD Pediatrics, DM Pediatric Clinical Immunology and Rheumatology (PGI, CHD)
*Giannina Gaslini Institute, Italy (Observership in Rheumatology)*
Consultant, Pediatric Immunologist and Rheumatologist, ASTER CMI Hospitals,
Bengaluru
*http://www.pediatricimmunologist.in/
<http://www.pediatricimmunologist.in/>*

*Aster CMI Hospital, No 43/2, International Airport Rd, Sahakara Nagar,
Bengaluru -560 092, Karnataka*
* (**Book appointment - 08043420100)*

On Sun, May 21, 2017 at 11:23 AM, CIS-PIDD <cis-pidd at lists.clinimmsoc.org>
wrote:

> Dear Sagar
>
> You need to check for G6PD  too .
>
> As severe G6PD may have  abnormal  DHR test .
>
> Best
>
>
>
> *Mehdi Adeli,*
> * MD, FAAAAI, FACAAI, FAAP, A.B.A.I, A.B.P*
> *Sr. Consultant Allergy & Immunology *
>
> *Assistant Professor Weill Cornell Medicine  -Qatar*
>
> *Pediatrics Department.*
>
> *Hamad Medical Corporation *
>
> *Sidra Medical And Research Center *
>
> *Tel (O) :( 974) 4439-0328*
>
> *Mob : (974) 6688 0048 /33429669.*
>
> *Fax: (974) 4439-7857*
>
> *E-Mail: madeli at hamad.qa <madeli at hmc.org.qa>*
>
> *Web : http://**aiap.hamad.qa <http://aiap.hamad.qa>*
>
> *Research Gate : http://www.researchgate.net/profile/Mehdi_Adeli
> <http://www.researchgate.net/profile/Mehdi_Adeli>*
>
> *ORCID ID:* *http://orcid.org/0000-0002-3051-3080
> <http://orcid.org/0000-0002-0346-5570>*
>
> [image: Untitled-1]
>
>
>
>
>
> *From:* cis-pidd at lyris.dundee.net [mailto:cis-pidd at lyris.dundee.net] *On
> Behalf Of *CIS-PIDD
> *Sent:* Friday, 19 May, 2017 4:45 PM
>
> *To:* CIS-PIDD
> *Subject:* Re: [cis-pidd] Rib abnormalities in CGD !!!
>
>
>
> Thanks Dr Aisha
>
>
>
> I shall repeat DHR once the child is better. Also the genetic tests would
> clarify the issue
>
>
>
> Regards
>
> Sagar
>
>
>
> On 19 May 2017 2:52 pm, "CIS-PIDD" <cis-pidd at lists.clinimmsoc.org> wrote:
>
> Dear Dr Sagar
>
>
>
> I had once a 4 m old girl (consanguineous parents) with Labs suggesting
> SCID and very defective DHR test as well.
>
> This patient was confirmed SCID: she had 3 homozygous RAG mutations:
>
> ·       *Molecular testing (Erasmus-2016): 3 homozygous RAG mutations – *
>
> o   *Homozygous RAG1 mutation: c.577G>a (p.Glu193Lys) – benign*
>
> o   *Homozygous RAG2 mutation: c.644C>T (p.Th215lle) – probably damaging*
>
> o   *Homozygous RAG2 mutation: c.686G>A (p.Arg229Gln) – probably damaging*
>
>
>
> We think our patient was a SCID patient. DHR is mentioned to be
> transiently abnormal during the course of a severe infection and reverts to
> normal thereafter. The patient died during her severe infection, allowing
> no chance to repeat DHR at another occasion.
>
> We had other patients with an abnormal DHR initially, but after resolution
> of the infection it reverted to normal. In our unit, we always confirm CGD
> diagnosed by DHR test by assessing NADPH oxidase component protein
> expression by flowcytometry.
>
>
>
> Aisha Elmarsafy
>
> Professor of Pediatrics/Chief of PID Unit
>
> Faculty of Medicine - Cairo University - Egypt
>
> Cell phone: +2 01223985147
>
> e-mail: aisha_mars at hotmail.com
>
>
> ------------------------------
>
> *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:* Thursday, May 18, 2017 10:03 AM
> *To:* CIS-PIDD
> *Subject:* Re: [cis-pidd] Rib abnormalities in CGD !!!
>
>
>
> Thanks for all the suggestions and inputs.
>
>
>
> NBT and DHR were performed on fresh samples. I am too surprised with the
> NBT and DHR results. I have asked for genetic testing with a panel that
> covers both SCID/omenn syndrome and CGD.
>
>
>
> I hope that shall settle the issue. Will update once I have the results
>
>
>
> Thanks again
>
>
>
>
> *Dr.Sagar Bhattad*
>
> MD Pediatrics, DM Pediatric Clinical Immunology and Rheumatology (PGI, CHD)
>
> *Giannina Gaslini Institute, Italy (Observership in Rheumatology)*
>
> Consultant, Pediatric Immunologist and Rheumatologist, ASTER CMI
> Hospitals, Bengaluru
>
>
>
> *Aster CMI Hospital, No 43/2, International Airport Rd, Sahakara Nagar,
> Bengaluru -560 092, Karnataka*
>
> * (**Book appointment - 08043420100**)*
>
>
>
> On Wed, May 17, 2017 at 9:26 PM, CIS-PIDD <cis-pidd at lists.clinimmsoc.org>
> wrote:
>
> Sagar:
>
> This sure sounds like Omenn or maternal GVHD.  Some thoughts:
>
>
>
> Did you have to ship the specimens for the DHR and NBT?
>
> Get DHR on mother.
>
> Can you get testing for maternal cells in baby’s circulation?
>
> Consider skin biopsy for evidence of GVHD.
>
>
>
> Very challenging case, good luck.
>
>
>
> Joe Church
>
> Children’s Hospital Los Angeles
>
>
>
>
>
> *From:* cis-pidd at lyris.dundee.net [mailto:cis-pidd at lyris.dundee.net] *On
> Behalf Of *CIS-PIDD
> *Sent:* Wednesday, May 17, 2017 7:37 AM
> *To:* CIS-PIDD
> *Subject:* RE: [cis-pidd] Rib abnormalities in CGD !!! (EXTERNAL EMAIL)
>
>
>
> Sorry for the typo error...
>
> CD3 is 58%
>
>
>
> DHR repeatef twice..... and is abnormal
>
> NBT is also abnormal.
>
>
>
> Will look for activation markers
>
>
>
> Thanks
>
>
>
> On 17 May 2017 8:01 pm, "CIS-PIDD" <cis-pidd at lists.clinimmsoc.org> wrote:
>
> There are many features in this patient that seem unusual for CGD – might
> be worth repeating the DHR test.  There also seems to be a significant
> deficit of lymphocytes if you add CD3, CD19, and CD56 – perhaps some type
> of Omenn syndrome?  Have you looked at activation markers on T cells – MHC
> Class II etc?
>
>
>
> Prescott
>
>
>
> T. Prescott Atkinson, MD PhD, Professor and Director
>
> Division of Pediatric Allergy, Asthma & Immunology
>
> University of Alabama at Birmingham
>
> Tel: 205-638-6457
>
> Fax: 205-975-7080
>
>
>
>
>
> *From:* cis-pidd at lyris.dundee.net [mailto:cis-pidd at lyris.dundee.net] *On
> Behalf Of *CIS-PIDD
> *Sent:* Wednesday, May 17, 2017 7:56 AM
> *To:* CIS-PIDD <cis-pidd at lyris.dundee.net>
> *Subject:* [cis-pidd] Rib abnormalities in CGD !!!
>
>
>
> Dear all
>
>
>
> I am Dr Sagar Bhattad, a clinical Immunologist at Bangalore, India.
>
>
>
> I need your expert opinion in the following case
>
>
>
> 4 months old boy
>
> Born of consanguineous wedlock
>
> Failure to thrive (birth weight 2.7 kg and at 4 months - 2.8 kg)
>
> Oral thrush
>
> Erythematous rash over trunk, face and limbs
>
> Loss of hairs over eyelids
>
> Hepatosplenomegaly, lymphadenopathy
>
>
>
> Investigations
>
> Absolute lymphocyte count - 3450
>
> Absolute eosinophil count - 9200
>
>
>
> CD3  33%
>
> CD19 23%
>
> CD56 10%
>
> CD4  26%
>
> CD8 7%
>
>
>
> IgG 568
>
> IgM 1094
>
> IgA  < 40
>
>
>
> IgE > 2500
>
>
>
> NBT - no reduction
>
>
>
> DHR - oxidative index 4.2 and control 102
>
>
>
> Abnormal NBT and DHR strongly suggest Chronic granulomatous disease
>
>
>
>
>
> *Other issues*
>
> Ribcage abnormality ------ bilateral several ribs look abnormal and are
> fused at places
>
>
>
> *Query*
>
> My clinical diagnosis in this child was *Omenn syndrome*. But abnormal
> NBT and DHR make me think of *CGD. *
>
>
>
> Can experts please opine on the diagnosis and the link with rib
> abnormalities
>
>
>
> Warm regards
>
> Sagar
>
>
>
>
>
>
>
>
>
>
>
>
>
>
> *Dr.Sagar Bhattad*
>
> MD Pediatrics, DM Pediatric Clinical Immunology and Rheumatology (PGI, CHD)
>
> *Giannina Gaslini Institute, Italy (Observership in Rheumatology)*
>
> Consultant, Pediatric Immunologist and Rheumatologist, ASTER CMI
> Hospitals, Bengaluru
>
>
>
> *Aster CMI Hospital, No 43/2, International Airport Rd, Sahakara Nagar,
> Bengaluru -560 092, Karnataka*
>
> * (**Book appointment - 08043420100**)*
>
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