[CIS PIDD] [CIS-PAGID] CVID Risk for children - further screening?

[Stan Ress]

How would it be best to monitor for future development of CVID in
children who have affected parents, and is genetic screening actually
warranted?
 
I have the following 3 scenarios:
 
1. A man contacted me about his 32 year-old wife who was diagnosed with
CVID & is getting monthly IVIG. I have no further details but I doubt
any genetic studies were done. He asked me about the risk for his 3 kids
aged 5 years, 3 years & 1 year & I indicated ~10%. Would one do periodic
serum Ig levels, or only test in the event of recurrent URTI's ?
 
2. I have 2 sisters diagnosed with CVID on IVIG therapy. Raising the
question of further screening of the family, I was told they are all
totally against this.
 
3. A related but distinct query. A young 16 year-old man with late
onset XLA (undiagnosed) presented with severe chest infection and
unfortunately died, despite AB therapy. He had absent B-cells on FCM,
very low IG levels, absent plasma cells on post-mortem, & confirmed gene
mutation: G to A transition at cDNA position 1574 (c, 1574G>A) in exon
16 of the BTK gene.
 
He has a younger brother. In this case, simply measuring circulating
B-cells & Ig levels in the sib should be adequate? Full genetic
screening, while of academic interest, is not affordable by this family,
& not offered by the state's public health care system.
 
I would value any advise in these situations.
 
Thanks & Regards,
 
Stan Ress

 
--
Stanley Ress
Associate Professor of Medicine
Head: Division of Clinical Immunology
Department of Medicine
H47 Old Main Building-room 26
Groote Schuur Hospital and UCT
Observatory 7925
Cape Town
South Africa
TEL:INTERN. + 2721-4066201 or 4066197
FAX:   "    + 2721-4486815
Cell: 0833115482 
email: stan.ress at uct.ac.za

>>> "Church, Joseph" <JChurch at chla.usc.edu> 2012/05/07 04:59 PM >>>

Thank you, Charlotte.  JC

-----Original Message-----
From: pagid-bounces at list.clinimmsoc.org
[mailto:pagid-bounces at list.clinimmsoc.org] On Behalf Of
Cunningham-Rundles, Charlotte
Sent: Monday, May 07, 2012 7:35 AM
To: PAGID
Subject: Re: [CIS-PAGID] CVID Risk for children

I agree with Mary Ellen.


>From our data,


I use the figure 8% overall for immune deficiency but of those only 2%
of the group have CVID in any other member, the rest were IgA
deficient.

Note the older literature that also says that the female is more likely
 (4x I think) to pass this on than the male with CVID.  Not something I
can address from our data, as we have more sibs with unaffected parents
than any other combination. 

As for TACI, the 50% rule does not really work as the majority have non
immune deficient family members ( one parent and sometimes a sib or
child) with the same mutation.


Charlotte Cunningham-Rundles, MD, PhD
Departments of Medicine and Pediatrics
The David S Gottesman Professor
The Immunology Institute
Mount Sinai School of Medicine
1425 Madison Avenue
New York, NY 10029
Phone: 212 659 9268
Fax: 212 987 5593
Email: Charlotte.Cunningham-Rundles at mssm.edu





> From: "Church, Joseph" <JChurch at chla.usc.edu>

> Reply-To: PAGID <pagid at list.clinimmsoc.org>

> Date: Mon, 7 May 2012 14:16:35 +0000

> To: PAGID <pagid at list.clinimmsoc.org>

> Subject: Re: [CIS-PAGID] CVID Risk for children

> 

> I thank you all for the very useful information.  JC

> 

> -----Original Message-----

> From: pagid-bounces at list.clinimmsoc.org 

> [mailto:pagid-bounces at list.clinimmsoc.org] On Behalf Of Conley, Mary



> Ellen

> Sent: Monday, May 07, 2012 7:11 AM

> To: pagid at list.clinimmsoc.org

> Subject: Re: [CIS-PAGID] CVID Risk for children

> 

> I use the same figure as Bodo - 10% but I come at it from a slightly



> different perspective.  Like Bodo, I consider the percentage of 

> patients with CVID who have affected family members.  But some of

that 

> 10% is not really CVID - it may be IgA deficiency or abnormal serum 

> immunoglobulins that are detected because of family studies rather 

> than repeated or unusual infections.  It may be autoimmune disease. 

I 

> also have a gut feeling, but no data, that with the sickest patients,

the risk may be a little higher.

> 

> Mary Ellen Conley, MD

> West Research Tower

> LeBonheur Children's Hospital

> 50 N. Dunlap St.

> Memphis TN  38103-2800

> Tel     901-287-4657

> FAX  901-287-4551

> mconley at uthsc.edu<mailto:mconley at uthsc.edu>

> 

> -----Original Message-----

> From: pagid-bounces at list.clinimmsoc.org 

> [mailto:pagid-bounces at list.clinimmsoc.org] On Behalf Of Grimbacher, 

> Bodo

> Sent: Saturday, May 05, 2012 4:34 PM

> To: pagid at list.clinimmsoc.org

> Subject: Re: [CIS-PAGID] CVID Risk for children

> 

> I tell my patients 10%.

> Why?

> A maximum of 10-20% of CVID patients are familial (10% in AD

families, 

> and suspected additional 10% with new mutations).

> So assuming 20% of CVID patients have a Mendelian form of CVID, and 

> most of them seem to be autosomal-dominant, I In AD traits the risk

of 

> any offspring is 50%.

> therefore arrive at an overall risk of 10% for an offspring of newly



> diagnosed CVID patients.

> Yours,

> Bodo Grimbacher

> CCI- Centre of Chronic Immunodeficiency Freiburg, GERMANY

> 

> 

> Am 05.05.12 01:27 schrieb "Church, Joseph" unter

<JChurch at chla.usc.edu>:

> 

>> Colleagues:

>> 

>> I just consulted on a 34yo man with probable CVID.  He and his wife



>> have no other medical issues.

>> 

>> They asked "what is the liklihood that their children (yet to be

>> conceived) will develop CVID?".

>> 

>> I would appreciate any insight (?data) you may have.

>> 

>> Thank you.

>> 

>> Joe Church

>> Children's Hospital Los Angeles

>> 

>> 

>> 

>>

---------------------------------------------------------------------

>> CONFIDENTIALITY NOTICE: This e-mail message, including any 

>> attachments, is for the sole use of the intended recipient(s) and

may 

>> contain confidential or legally privileged information. Any 

>> unauthorized review, use, disclosure or distribution is prohibited.



>> If you are not the intended recipient, please contact the sender by



>> reply e-mail and destroy all copies of this original message.

>> 

>>

---------------------------------------------------------------------

>> 

> 

> 

> 

> 

> 

>

---------------------------------------------------------------------

> CONFIDENTIALITY NOTICE: This e-mail message, including any 

> attachments, is for the sole use of the intended recipient(s) and may



> contain confidential or legally privileged information. Any 

> unauthorized review, use, disclosure or distribution is prohibited.

If 

> you are not the intended recipient, please contact the sender by

reply 

> e-mail and destroy all copies of this original message.

> 

>

---------------------------------------------------------------------

> 





---------------------------------------------------------------------
CONFIDENTIALITY NOTICE: This e-mail message, including any attachments,

is for the sole use of the intended recipient(s) and may contain
confidential
or legally privileged information. Any unauthorized review, use,
disclosure
or distribution is prohibited. If you are not the intended recipient,
please
contact the sender by reply e-mail and destroy all copies of this
original message.  

---------------------------------------------------------------------






###

UNIVERSITY OF CAPE TOWN 

This e-mail is subject to the UCT ICT policies and e-mail disclaimer
published on our website at
http://www.uct.ac.za/about/policies/emaildisclaimer/ or obtainable from
+27 21 650 9111. This e-mail is intended only for the person(s) to whom
it is addressed. If the e-mail has reached you in error, please notify
the author. If you are not the intended recipient of the e-mail you may
not use, disclose, copy, redirect or print the content. If this e-mail
is not related to the business of UCT it is sent by the sender in the
sender's individual capacity.

###
 
-------------- next part --------------
An HTML attachment was scrubbed...
URL: <http://seven.pairlist.net/mailman/private/pagid/attachments/20120604/be76e723/attachment.htm>