[CIS-PAGID] ADA deficiency hearing loss

[Nicholas Rider]

Hi Fabio,

Interesting data, thank you for communicating it to the group.  As you  
said, it's tough to know whether CNS purine load is at all affected by  
PEG-ADA.  Do you know if the measured ABR and audiometry changed after  
starting PEG-ADA in your patients?  Was the improvement at all  
correlated with plasma adenosine metabolite levels?

Thanks,

Nick

Nicholas L. Rider, D.O.
Clinic for Special Children
535 Bunker Hill Road
Strasburg, PA 17579
Ph:  717-687-9407
Fx:   717-687-9237
nrider at clinicforspecialchildren.org



On May 27, 2011, at 6:17 PM, Candotti, Fabio (NIH/NHGRI) [E] wrote:


> Seven of the sixteen patients who had audiology evaluation here at  

> NIH were found to have mild to severe hearing loss.  In some cases  

> the hearing loss improved soon after PEG-ADA enzyme replacement  

> therapy was initiated, but it did not avoid the subsequent need for  

> hearing aids.  In some patients, the hearing loss became more severe  

> with time while on PEG-ADA, similar to Dr. Wasserman's case.

> I think it's safe to say we do no know the basis for this  

> complication.  Back in 1980, Rochelle Hirschhorn proposed that  

> neurologic abnormalities in ADA deficiency may be due to  

> intracerebral accumulation of purine substrates.  High  

> concentrations of adenosine interacting with the A1 receptors in the  

> nervous tissue may be responsible.  One would assume, however, that  

> adenosine is low in PEG-ADA treated patients, although that is not  

> an easy measurement to obtain.  To my knowledge, an autoimmune cause  

> for hearing loss in ADA deficiency has not be proposed, yet...

>

> Fabio

>

> ==================================

> Fabio Candotti, MD

> Head, Disorders of Immunity Section

> Genetics and Molecular Biology Branch

> National Human Genome Research Institute

> National Institutes of Health

> 49 Convent Dr.

> Blg. 49, Rm 3A04, MSC 4442

> Bethesda, MD  20892-4442

>

> Tel: (301) 435 2944 - (301) 402 2347

> Fax: (301) 480 3678

> E-mail: fabio at nhgri.nih.gov

> ==================================

>

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>

> On 5/26/11 4:35 PM, "Junker, Anne" <Anne.Junker at phsa.ca> wrote:

>

> I was a guest consultant at another centre where a child was  

> presented a few years ago - this is the email response to my query  

> today, based on your post.  anne

>

> Yes, the child (now age 15) does have hearing loss and wears hearing  

> aids.  I do think that the hearing loss is likely a component of the  

> "ADA syndrome".  In addtion, the patient, who received gene therapy,  

> has multiple other medical concerns including visual impairment,  

> precocious puberty, features of autism, bone changes and multiple  

> hematologic changes (cytopenias, stippling of certain cell lines).   

> The NIH team, I am told, is about to report on their collection of  

> gene therapy patients.  The NIH group would likely have more insight  

> into the hearing changes in these patients.

>

>

> Anne K. Junker, MD, FRCP(C)

> Associate Professor, Pediatrics

> Director, Clinical Immunology Service, BC Children's Hospital

> Director, Clinical & Population Studies, Child & Family Research  

> Institute

> Director, Maternal Infant Child Youth Research Network of Canada/ 

> Reseau de Recherche en Sante des Enfant et des Meres (MICYRN)

> K4-223 4480 Oak Street

> Vancouver, British Columbia

> Canada  V6H 3V4

> phone: 604-875-3591

> fax: 604-875-2414

> email: ajunker at cw.bc.ca

>

>

>

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

> ] On Behalf Of Richard Wasserman

> Sent: Thursday, May 26, 2011 1:33 PM

> To: pagid at list.clinimmsoc.org

> Subject: Re: [CIS-PAGID] ADA deficiency hearing loss

>

> He has not had an MRI in several years. The hearing loss has been  

> slowly, but steadily progressive for many years. There is no  

> vertigo. There are no other neurologic findings. He has been fully  

> treated with Adagen since age 2.

> Richard Wasserman

>

> 2011/5/26 Sanchez Ramon.Silvia <ssanchez.hgugm at salud.madrid.org>

> Has he demyelinating lesions on brain MRI? is deafness fluctuating,  

> with vertigo?

>

> Silvia SÁNCHEZ-RAMÓN, MD, PhD

> Unidad de Inmunología Clínica

> Servicio de Inmunología

> Hospital General Universitario Gregorio Marañón

> Calle Doctor Esquerdo, 46

> E- 28007 - Madrid, Spain

> Tel: +34 914265181 <tel:%2B34%20914265181>

> FAX: +34 915868018 <tel:%2B34%20915868018>

> E-mail: ssanchez.hgugm at salud.madrid.org

> ________________________________________

> De: pagid-bounces at list.clinimmsoc.org [pagid-bounces at list.clinimmsoc.org 

> ] En nombre de Richard Wasserman [drrichwasserman at gmail.com]

> Enviado el: jueves, 26 de mayo de 2011 17:34

> Para: PAGID

> Asunto: [CIS-PAGID] ADA deficiency hearing loss

>

>

> I care for a 13 year old with ADA deficiency doing well on Adagen  

> who has progressive hearing loss. I know that this is a recognized  

> association. He is getting a cochlear implant and the otologist has  

> made a diagnosis of otic neuropathy. Is the pathogenesis of hearing  

> loss in ADA deficiency known? Is there any suggestion of  

> autoimmunity as a cause?

> Thanks,

> Richard Wasserman

>

> --

> Richard L. Wasserman, MD, PhD

> DallasAllergyImmunology

> 7777 Forest Lane, Suite B-332

> Dallas, Texas 75230

> Office (972) 566-7788 <tel:%28972%29%20566-7788>

> Fax (972) 566-8837 <tel:%28972%29%20566-8837>

> Cell (214) 697-7211 <tel:%28214%29%20697-7211>

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