Clinical and economic aspects of newborn screening for severe combined immunodeficiency: DEPISTREC study results

Thomas, Caroline; Durand‐Zaleski, Isabelle; Frenkiel, J.; Mirallié, S.; Léger, Alexandra; Cheillan, David; Pïcard, Capucine; Mahlaoui, Nizar; Riche, Valéry-Pierre; Roussey, M.; Sébille, Véronique; Rabetrano, Hasina; Dert, Cécile; Fischer, Alain; Audrain, Marie

doi:10.1016/j.clim.2019.03.012

Cited by 37 publications

(51 citation statements)

References 18 publications

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“…In light of these statistics, unrecognized infant PID mortality may significantly contribute to the low prevalence of PID in Russia, as patients die before they are diagnosed with PID. Thus, future introduction of neonatal PID screening utilizing TREC/KREC detection may substantially improve PID verification (19,20).…”

Section: Discussionmentioning

confidence: 99%

Primary Immunodeficiencies in Russia: Data From the National Registry

et al. 2020

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Introduction: Primary immunodeficiencies (PID) are a group of rare genetic disorders with a multitude of clinical symptoms. Characterization of epidemiological and clinical data via national registries has proven to be a valuable tool of studying these diseases. Materials and Methods: The Russian PID registry was set up in 2017, by the National Association of Experts in PID (NAEPID). It is a secure, internet-based database that includes detailed clinical, laboratory, and therapeutic data on PID patients of all ages. Results: The registry contained information on 2,728 patients (60% males, 40% females), from all Federal Districts of the Russian Federation. 1,851/2,728 (68%) were alive, 1,426/1,851 (77%) were children and 425/1,851 (23%) were adults. PID was diagnosed before the age of 18 in 2,192 patients (88%). Antibody defects (699; 26%) and syndromic PID (591; 22%) were the most common groups of PID. The minimum overall PID prevalence in the Russian population was 1.3:100,000 people; the estimated PID birth rate is 5.7 per 100,000 live births. The number of newly diagnosed patients per year increased dramatically, reaching the maximum of 331 patients in 2018. The overall mortality rate was 9.8%. Genetic testing has been performed in 1,740 patients and genetic defects were identified in 1,344 of them (77.2%). The median diagnostic delay was 2 years; this varied from 4 months to 11 years, depending on the PID category. The shortest time to diagnosis was noted in the combined PIDs-in WAS, DGS, and CGD. The longest delay was observed in AT, NBS, and in the most prevalent adult PID: HAE and CVID. Of the patients, 1,622 had symptomatic treatment information: 843 (52%) received IG treatment, mainly IVIG (96%), and 414 (25%) patients were treated with biological drugs. HSCT has been performed in 342/2,728 (16%) patients, of whom 67% are currently alive, 17% deceased, and 16% lost to follow-up. Three patients underwent gene therapy for WAS; all are currently alive. Conclusions: Here, we describe our first analysis of the epidemiological features of PID in Russia, allowing us to highlight the main challenges around PID diagnosis and treatment.

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Section: Discussionmentioning

confidence: 99%

Primary Immunodeficiencies in Russia: Data From the National Registry

et al. 2020

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“…A quicker diagnosis allows earlier genotype-specific treatments (e.g., HSCT) prior to life-threatening infections, which offers a better outcome and improves the quality of life ( 49 – 51 ). This will also significantly reduce the costs of delayed diagnosis and treatment of related morbidities ( 52 – 54 ). We have shown a good correlation between the TREC results using our established assay with the CDC in-house method, indicating this assay is potentially applicable for the NBS program for severe PIDD.…”

Section: Discussionmentioning

confidence: 99%

Establishing Simultaneous T Cell Receptor Excision Circles (TREC) and K-Deleting Recombination Excision Circles (KREC) Quantification Assays and Laboratory Reference Intervals in Healthy Individuals of Different Age Groups in Hong Kong

Kwok

Cheung

et al. 2020

Front. Immunol.

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The clinical experience gathered throughout the years has raised awareness of primary immunodeficiency diseases (PIDD). T cell receptor excision circles (TREC) and kappa-deleting recombination excision circles (KREC) assays for thymic and bone marrow outputs measurement have been widely implemented in newborn screening (NBS) programs for Severe Combined Immunodeficiency. The potential applications of combined TREC and KREC assay in PIDD diagnosis and immune reconstitution monitoring in non-neonatal patients have been suggested. Given that ethnicity, gender, and age can contribute to variations in immunity, defining the reference intervals of TREC and KREC levels in the local population is crucial for setting up cutoffs for PIDD diagnosis. In this retrospective study, 479 healthy Chinese sibling donors (240 males and 239 females; age range: 1 month−74 years) from Hong Kong were tested for TREC and KREC levels using a simultaneous quantitative real-time PCR assay. Age-specific 5 th-95 th percentile reference intervals of TREC and KREC levels (expressed in copies per µL blood and copies per 10 6 cells) were established in both pediatric and adult age groups. Significant inverse correlations between age and both TREC and KREC levels were observed in the pediatric age group. A significant higher KREC level was observed in females than males after 9-12 years of age but not for TREC. Low TREC or KREC levels were detected in patients diagnosed with mild or severe PIDD. This assay with the established local reference intervals would allow accurate diagnosis of PIDD, and potentially monitoring immune reconstitution following haematopoietic stem cell transplantation or highly active anti-retroviral therapy in the future.

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“…The pilot study in France (DEPISTREC) compared a group of 190,517 babies who underwent TREC screening with a control group of 1,400,000 babies and both clinical and economic aspects were investigated (20, 21). Via TREC screening three patients with SCID were identified vs. 28 in the control group, of whom five children died from SCID before they could receive HSCT, which could have been prevented by TREC screening.…”

Section: Pilot Programs Addressing Additional Aspects Of Screeningmentioning

confidence: 99%

Universal Newborn Screening for Severe Combined Immunodeficiency (SCID)

et al. 2019

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Patients with severe combined immunodeficiency (SCID) are born with profound deficiency of functional T-lymphocytes. Early detection and diagnosis would allow for prompt institution of isolation from infection and referral for definitive treatment with allogeneic hematopoietic stem cell transplantation. Universal newborn screening for SCID, using an assay to detect T-cell receptor excision circles (TREC) in dried blood spots (DBS), is now being performed in all states in the United States. In this review, we discuss the development and outcomes of TREC screening, and continued challenges to implementation.

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Clinical and economic aspects of newborn screening for severe combined immunodeficiency: DEPISTREC study results

Cited by 37 publications

References 18 publications

Primary Immunodeficiencies in Russia: Data From the National Registry

Primary Immunodeficiencies in Russia: Data From the National Registry

Establishing Simultaneous T Cell Receptor Excision Circles (TREC) and K-Deleting Recombination Excision Circles (KREC) Quantification Assays and Laboratory Reference Intervals in Healthy Individuals of Different Age Groups in Hong Kong

Universal Newborn Screening for Severe Combined Immunodeficiency (SCID)

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