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

[Church, Joseph]

Please see below.
Joe Church
From: pagid-bounces at list.clinimmsoc.org [mailto:pagid-bounces at list.clinimmsoc.org] On Behalf Of Stan Ress
Sent: Monday, June 04, 2012 2:53 AM
To: pagid at list.clinimmsoc.org
Subject: Re: [CIS PIDD] [CIS-PAGID] CVID Risk for children - further screening?

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 ? I would wait, but would not hesitate at the early development of symptoms.

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. Again, I would wait for symptoms.

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? Yes.  Full genetic screening, while of academic interest, is not affordable by this family, & not offered by the state's public health care system.  We had a similar situation with an 9yo boy who had recurrent pneumonias and developed bronchiectasis before a diagnosis of XLA was made.  His 3+yo brother was asymptomatic.  Both had absent B-cells and the same BTK mutation.

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<mailto:stan.ress at uct.ac.za>

>>> "Church, Joseph" <JChurch at chla.usc.edu<mailto: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<mailto:Charlotte.Cunningham-Rundles at mssm.edu>





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

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

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

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

> [mailto:pagid-bounces at list.clinimmsoc.org]<mailto:[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<mailto: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<mailto:mconley at uthsc.edu%3cmailto:mconley at uthsc.edu>>

>

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

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

> [mailto:pagid-bounces at list.clinimmsoc.org]<mailto:[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<mailto: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<mailto: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

>>

>>

>>

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>

>

>

>

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