Bilateral sensorineural deafness in adenosine deaminase-deficient severe combined immunodeficiency

Albuquerque, Wendy; Gaspar, H. Bobby

doi:10.1016/j.jpeds.2003.10.055

Cited by 69 publications

(47 citation statements)

References 9 publications

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“…9,10 ADA is known to be expressed systemically and other nonimmunologic deficits, including audiologic, hepatic, renal, and skeletal abnormalities, are well documented. [23][24][25][26] We also show that in addition to previously described motor neurologic defects, 27 children with Chédiak-Higashi syndrome have severe cognitive problems. The LYST protein defective in Chédiak-Higashi syndrome is ubiquitously expressed and is involved in controlling exocytosis of secretory granules, and its absence may therefore disturb neuronal lysosomal trafficking.…”

Section: Discussionmentioning

confidence: 57%

Cognitive and behavioral abnormalities in children after hematopoietic stem cell transplantation for severe congenital immunodeficiencies

Titman

Pink

Skucek

et al. 2008

Blood

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Section: Discussionmentioning

confidence: 57%

Cognitive and behavioral abnormalities in children after hematopoietic stem cell transplantation for severe congenital immunodeficiencies

Titman

Pink

Skucek

et al. 2008

Blood

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“…15,23 There is also a high incidence of audiologic defects, typically bilateral high-frequency sensorineuronal hearing loss. 24 These abnormalities do not correlate with any specific type of transplantation, the conditioning regimen, degree of donor cell engraftment, or metabolite levels after HSCT. However, IQ was shown to correlate with the level of dATP (and by inference the degree of metabolic derangement) at the time of diagnosis, which may indicate that irreversible damage had occurred in the early neonatal period.…”

Section: Hsctmentioning

confidence: 97%

“…10 The ubiquitous nature of ADA expression, however, does lead to a number of significant nonimmunologic defects. ADA-SCID patients have costochondral abnormalities and skeletal dysplasias, 11 neurologic deficits involving motor function, 12 bilateral sensorineuronal deafness, 13 and hepatic dysfunction. 14 ADA-SCID patients show defects in cognitive and behavioral function despite correction of immunologic abnormalities after bone marrow transplantation, 15 thus highlighting the systemic nature of the disease.…”

Section: Ada-scidmentioning

confidence: 99%

How I treat ADA deficiency

Gaspar

Aiuti

Porta

et al. 2009

Blood

191

208

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Adenosine deaminase deficiency is a disorder of purine metabolism leading to severe combined immunodeficiency (ADA-SCID). Without treatment, the condition is fatal and requires early intervention. Haematopoietic stem cell transplantation is the major treatment for ADA-SCID, although survival following different donor sources varies considerably. Unlike other SCID forms, 2 other options are available for ADA-SCID: enzyme replacement therapy (ERT) with pegylated bovine ADA, and autologous haematopoietic stem cell gene therapy (GT). Due to the rarity of the condition, the lack of large scale outcome studies, and availability of different treatments, guidance on treatment strategies is limited. We have reviewed the currently available evidence and together with our experience of managing this condition propose a consensus management strategy. IntroductionAdenosine deaminase (ADA) deficiency is a rare inherited disorder of purine metabolism characterized by the accumulation of metabolic substrates that lead to abnormalities of immune system development and function and a variety of systemic defects. The initial and most devastating presentation of the disease is the result of the immune defects; affected infants characteristically present with severe opportunistic infection and failure to thrive and an immunologic profile consistent with severe combined immunodeficiency (ADA-SCID). Without treatment, the condition is fatal in the first year of life and therefore necessitates early intervention. Allogeneic hematopoietic stem cell transplantation (HSCT) has long been considered the mainstay of treatment of ADA-SCID. However, unlike other SCID forms, 2 other treatment options are available for ADA-SCID, namely, enzyme replacement therapy (ERT) with pegylated bovine ADA (Pegadamase, Adagen, or PEG-ADA) and autologous HSC gene therapy (GT).The availability of different treatment modalities presents an opportunity for improved patient care but also presents difficulties in deciding on the specific choice of treatment for individual patients. Making the correct choice is further complicated by the fact that ADA deficiency is not purely an immune defect, unlike other SCID forms, and the systemic manifestations, which can be of major clinical consequence, must also be managed. The rarity of the condition (estimated at anything from 1:200 000 to 1:1 million births) means that any one center has access to only small numbers of patients precluding large-scale prospective studies from which formal and robust outcome data can be accrued. For these reasons, we have gathered experts with experience in management of patients using the different treatment modalities to collect and review the available retrospective data and to construct a consensus management strategy that may be of use to physicians managing this difficult patient population. ADA-SCIDSCID arises from a variety of molecular defects that have profound effects on lymphocyte development and function, including defects in the lymphocyte-specific signaling molecules (comm...

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“…This is important not only for monitoring the durability of the immune reconstitution achieved but also for screening for nonhematopoietic complications. Among the latter, we monitor for hearing deficit, which may be part of the original disorder, as in ADA SCID, 65 or a consequence of the HSCT procedure; dental defects as previously described 66 ; endocrine and fertility deficits in those receiving conditioning chemotherapy; and, importantly, neurobehavioral disorders, which we have shown to be potential problems in this group of patients. 64,67 Most families will want genetic and family planning counseling.…”

Section: Follow-upmentioning

confidence: 99%

How I treat severe combined immunodeficiency

Gaspar

Qasim

Davies

et al. 2013

Blood

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Severe combined immunodeficiency (SCID) arises from different genetic defects associated with lymphocyte development and function and presents with severe infections. Allogeneic hematopoietic stem cell transplantation is an extremely effective way of restoring immunity in these individuals. Numerous multicenter studies have identified the factors determining successful outcome, and survival for SCID has shown great improvement. Advances in understanding the genetic basis of disease also mean that we increasingly tailor transplant protocols to the specific SCID form. Wherever possible, we attempt to transplant SCID patients without the use of cytoreductive conditioning, but it is clear that this is only successful for specific SCID forms and, although survival is good, in specific patients there are ongoing humoral defects. We aim to use matched related and unrelated donors (including cord blood) whenever possible and have limited the use of mismatched haploidentical donors. The development of autologous hematopoietic stem cell gene therapy provides another treatment of the X-linked and adenosine deaminase–deficient forms of SCID, and we discuss how we have integrated gene therapy into our treatment strategy. These developments together with the advent of universal newborn screening for SCID should allow for a highly favorable outcome for this otherwise lethal condition.

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Bilateral sensorineural deafness in adenosine deaminase-deficient severe combined immunodeficiency

Cited by 69 publications

References 9 publications

Cognitive and behavioral abnormalities in children after hematopoietic stem cell transplantation for severe congenital immunodeficiencies

Cognitive and behavioral abnormalities in children after hematopoietic stem cell transplantation for severe congenital immunodeficiencies

How I treat ADA deficiency

How I treat severe combined immunodeficiency

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