Tandem mass spectrometric determination of purine metabolites and adenosine deaminase activity for newborn screening of ADA–SCID

Al-Dirbashi, Osama Y.; Ogrel, Svetlana; McIntosh, Nathan; Higgins, Lauren; McRoberts, Christine; Fisher, L. Megan; Bulman, Dennis E.; Geraghty, Michael T.; Chakraborty, Pranesh

doi:10.14785/lpsn-2014-0024

Cited by 7 publications

(11 citation statements)

References 19 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Ado and dAdo (normal values <3.0 and 0.4 mmol/L, respectively) were measured before 0.5 months of life. 4 HSCT was performed as previously described. 5 ERT using Adagen (Sigma-Tau Pharmaceuticals, Gaithersburg, Md) was administered in accordance with the manufacturer's instructions.…”

mentioning

confidence: 99%

“…2,3 The introduction and now nearcomplete adoption of population-based newborn screening (NBS) for SCID in the United States has led to earlier diagnosis of both typical SCID and atypical, or leaky, forms of these diseases, the latter caused by hypomorphic gene defects that allow a small amount of gene function with a consequently varied spectrum of immune defects, including Omenn syndrome. 4 Unique clinical features of particular genetic subtypes of SCID, such as increased sensitivity to radiation and alkylating chemotherapy in patients with Artemis/DCLRE1C deficiency, impact outcome following allogeneic hematopoietic cell transplantation (HCT) including survival, immune reconstitution, and late effects. 1,5 The Primary Immune Deficiency Treatment Consortium (PIDTC) 6901 Prospective Study has been enrolling patients with SCID disorders in the United States and Canada since August 2010.…”

mentioning

confidence: 99%

See 1 more Smart Citation

Neutropenia among patients with adenosine deaminase deficiency

Kim

Pham‐Huy

Grunebaum

2019

Journal of Allergy and Clinical Immunology

View full text Add to dashboard Cite

(ADA) is a ubiquitous enzyme important for the degradation and salvage of adenosine (Ado) and deoxyAdo (dAdo). Autosomal-recessive defects that severely disrupt the function of ADA lead to accumulation of purine metabolites, which are toxic for rapidly proliferating cells, such as lymphocytes. 1 Most ADA-deficient patients present in the first year of life with profound T-and B-cell defects, leading to severe combined immunodeficiency (SCID). In addition, ADA-deficient patients frequently suffer from liver, lungs, bone, and other tissues abnormalities. 1 Management of ADA deficiency includes supportive care with antimicrobials such as trimethoprim/ sulfamethoxazole (TMP-SMZ) and immunoglobulins. Enzyme replacement therapy (ERT) with polyethylene-glycol-conjugated ADA can improve purine homeostasis and may serve as a ''bridge'' until patients undergo allogeneic hematopoietic stem cell transplantation (HSCT) or gene therapy (GT). HSCT using healthy HLA-matched or mismatched family-related or unrelated donors can correct the immune and some of the systemic abnormalities. 2 Myelodysplasia has previously been reported among ADA-deficient patients; however, because most patients were after unsuccessful HSCT or GT, the role of the metabolic abnormality was not clear. 3 Here, we tested the hypothesis that ADA deficiency could be directly associated with myeloid abnormalities and neutropenia. We analyzed data from all 20 patients diagnosed at our center

show abstract

mentioning

confidence: 99%

mentioning

confidence: 99%

Neutropenia among patients with adenosine deaminase deficiency

Kim

Pham‐Huy

Grunebaum

2019

Journal of Allergy and Clinical Immunology

View full text Add to dashboard Cite

show abstract

“…Subjects include the parents of patients recently described with homozygous RelB mutations (Merico et al 2015). Patient data were compiled prospectively and retrospectively from medical records and were entered into the Canadian Centre for Primary Immunodeficiency Registry and tissue bank, which was approved by the SickKids Research Ethics Board (protocol # 1000005598).…”

Section: Subjectsmentioning

confidence: 99%

“…Father 1 (F1) and Mother 1 (M1) are both of Irish descent and are the parents of patients 1 and 2 as described in Merico et al (2015). Medical history was remarkable for asthma in F1 and psoriasis and atopic dermatitis in M1.…”

Section: Case Reportsmentioning

confidence: 99%

“…Specifically, mutations in NFĸB Essential Modulator (NEMO, also known as inhibitor factor of nuclear factor kappa-B kinase subunit gamma (IKKγ)), IĸBα, and inhibitor of NFĸ-B kinase subunit beta (IKKβ, also known as IKK2) have been described (Doffinger et al 2001;Courtois et al 2003;Janssen et al 2004;Orange et al 2004;Lopez-Granados et al 2008;Picard et al 2011;Pannicke et al 2013;Schimke et al 2013). Recently, Merico et al (2015) described homozygous mutations in the gene encoding RelB (c.1191 C > A; Y397 stop) resulting in the premature stop and the ablation of RelB expression. The 3 patients described had features of combined immunodeficiency with repeated infections and failure to thrive.…”

Section: Introductionmentioning

confidence: 99%

See 1 more Smart Citation

Heterozygous mutations in RelB can be associated with immune dysregulation and lymphoma

2016

View full text Add to dashboard Cite

Background: The nuclear factor kappa-B (NFκB) family of transcription factors is essential for numerous processes, including the development and function of the innate and adaptive immune response, inflammation and cell growth, differentiation, and survival. Recently, patients with homozygous mutations in the gene for the NFκB transcription factor RelB have been described as presenting with features of combined immunodeficiency such as recurrent infection and failure to thrive as well as reduced response to mitogens and an inability to maintain an adequate antibody response to immunizations. Methods: The immune status and genetics of the parents of patients with homozygous RelB mutations were assessed. In vitro mitogen stimulation, flow cytometry, and cytokine ELISA were used to assess immunological status and signal transduction pathways. Results: Four patients were confirmed to have heterozygous RelB mutations. The majority of patients had evidence of immune dysfunction with impaired in vitro responses to PHA and antigens. One patient developed lymphoma. Conclusion: Heterozygous RelB mutations can be associated with immune dysregulation with impaired mitogen and antigen responses and lymphoma. It is likely that the immune defects apparent in RelB deficient humans are due to a wider effect of RelB on the classical NFκB pathway (involving RelA and c-Rel) through cross-regulation of activation and expression in addition to RelB’s function within the alternate pathway. Statement of novelty: We describe for the first time the immune abnormalities in patients with heterozygous RelB mutations.

show abstract

Newborn Screening in the Diagnosis of Primary Immunodeficiency

Kobrynski

2021

Clinic Rev Allerg Immunol

View full text Add to dashboard Cite

Newborn screening for severe combined immune deficiency (SCID) is the first inborn error of immunity (IEI) to be detected through population screening. It also represents the first newborn screening test to utilize molecular testing on DNA from newborn dried blood spots. Newborn screening for SCID has provided opportunities to measure the population prevalence of this disorder and evaluate the effect of early interventions on the overall outcomes in affected infants. The success of SCID newborn screening has increased interest in developing and implementing molecular testing for other clinically significant inborn errors of immunity. This methodology has been adapted to screen for another monogenic inborn defect, spinal muscle atrophy. Advances in the clinical care and new therapeutics for many inborn errors of immunity support the need for early diagnosis and prompt institution of therapies to reduce morbidity and mortality. Early diagnosis may also improve the quality of life for affected patients. This article provides an overview of newborn screening for SCID, recommended steps for follow-up testing and early intervention as well as long-term follow-up. Numerous challenges remain, including the development of clinical consensus regarding confirmatory and diagnostic testing, early interventions, and best practices for immune reconstitution in affected infants.

show abstract

Tandem mass spectrometric determination of purine metabolites and adenosine deaminase activity for newborn screening of ADA–SCID

Cited by 7 publications

References 19 publications

Neutropenia among patients with adenosine deaminase deficiency

Neutropenia among patients with adenosine deaminase deficiency

Heterozygous mutations in RelB can be associated with immune dysregulation and lymphoma

Newborn Screening in the Diagnosis of Primary Immunodeficiency

Contact Info

Product

Resources

About