[CIS-PAGID] ADA deficiency hearing loss

[Candotti, Fabio (NIH/NHGRI) [E]]

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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