Incidence Of Severe Combined Immunodeficiency Research Articles

Severe Combined Immunodeficiency (SCID) in Canadian Children: A National Surveillance Study

PurposeSevere Combined Immune Deficiency (SCID) is universally fatal unless treated with hematopoietic stem cell transplantation (HSCT). Following the identification of disseminated Bacille Calmette-Guérin (BCG) infections in Canadian First Nations, Métis and Inuit (FNMI) children with unrecognized primary immune deficiencies, a national surveillance study was initiated in order to determine the incidence, diagnosis, treatment and outcome of children with SCID in Canada.MethodsCanadian pediatricians were asked to complete a monthly reporting form if they had seen a suspected SCID case, from 2004 to 2010, through the Canadian Paediatric Surveillance Program (CPSP). If the case met CPSP SCID criteria, more detailed data, including demographics and clinical information about investigations, treatment and outcome was collected.ResultsA total of 40 cases of SCID were confirmed for an estimated incidence of SCID in non-FNMI Canadian children of 1.4 per 100,000 live births (95 % CI 1 to 1.9/100,000). The proportion of SCID cases that were FNMI (17.5 %) was almost three times higher than was expected on the basis of proportion of the pediatric population estimated to be FNMI (6.3 %) resulting in an estimated incidence of 4.4 per 100,000 live births (95 % CI 2.1 to 9.2/100,000) in FNMI Canadian children. The mean age at diagnosis for all SCID cases was 4.2 months (range 1–583 days). There were 12 deaths (30 %; 95 % CI 18–46 %); seven died of confirmed or suspected infections before they could receive an HSCT.ConclusionsThe frequency of SCID cases in FNMI children is higher than in the general Canadian pediatric population. The high mortality rate, due primarily to infection, suggests that early diagnosis by newborn screening followed by HSCT could significantly benefit children with SCID.

Incidence of severe combined immunodeficiency through newborn screening in a Chinese population.

In order to know the true incidence of severe combined immunodeficiency (SCID) in a Chinese population, we conducted and implemented SCID newborn screening in Taiwan. Between May 1, 2010 and December 31, 2011, the National Taiwan University Hospital Newborn Screening Center screened all newborns for T-cell lymphopenia by measuring the copy number of T-cell receptor excision circles (TRECs) and RNase P. Newborns with low TREC values were subjected to complete blood cell counts and flow cytometry. A total of 106,391 newborns were screened using the TREC assay over a period of 19 months. Five newborns were immediately referred for confirmatory tests, including two SCID patients and two patients with persistent T-cell lymphopenia; a third SCID patient was found 2 months after the study period. All three SCID cases received stem cell transplantation at the age of 2-5 months. We also identified five cases of 22q11.2 microdeletion syndrome. During this period, two SCID patients from among the unscreened newborns were reported, and they died at ages 3 months and 4 months, respectively. Newborn screening to measure the number of TREC copies successfully identifies newborns with T-cell lymphopenia, 22q11.2 microdeletion syndrome, and other high-risk conditions. Taken together, the incidence of T-cell lymphopenia in apparently healthy newborns is more than 1 in 11,821, and further attention to their immune functions is warranted.

Advances in basic and clinical immunology in 2010

Reports in basic and clinical immunology in 2010 reflected the use of state-of-the-art genetic and immunologic tools to characterize the pathogenesis of immunologic diseases and the development of novel therapies directed to these conditions. B-cell biology has been explained in greater detail, significantly with lessons from the genetic defects found in the humoral immunodeficiencies. Therapeutic mAbs are given for an increasing number of indications, such as anti-CD20 antibodies or rituximab, which was initially developed for non-Hodgkin lymphomas and is currently used in diverse autoimmune and inflammatory disorders. The report of an infant with severe combined immunodeficiency (SCID) in Massachusetts detected by means of newborn screening and successfully treated with hematopoietic stem cell transplantation validated recent efforts toward newborn screening for SCID. Improvement of survival outcomes for patients with primary immunodeficiencies treated with hematopoietic stem cell transplantation was demonstrated in a large European cohort, with significant appreciation of the type of donor graft, particularly the use of HLA-matched unrelated donors for patients with non-SCID. Progress in cellular mechanisms of drug hypersensitivity included the characterization of nitroso-modified drug metabolites as potent T-cell activators and the identification of the relocation of plasmacytoid dendritic cells from blood to skin as a potential risk factor for reactivation of viral disease.

Why Newborn Screening for Severe Combined Immunodeficiency Is Essential: A Case Report

Physicians caring for infants in the first months of life need to know the normal ranges for absolute lymphocyte counts (ALCs) during that age. Any ALC <2500/microL is potentially pathogenic in early infancy and should be evaluated. We report the case of a 4-month-old white girl with a 2-month history of an oral ulcer, intermittent fever, recurrent otitis, decreased appetite, weight loss, and a new respiratory illness with hypoxemia. She had been in an in-home day care since birth. The patient's primary care physician had seen her frequently and obtained blood counts, but her persistent lymphopenia had not been appreciated. The infant was ultimately diagnosed with T(-)B(-)NK(+) (lacking both B and T lymphocytes and having primarily natural killer [NK] cells), recombinase-activating gene 2 (RAG2)-deficient severe combined immunodeficiency (SCID). However, because she had already developed 2 difficult-to-treat viral infections (parainfluenza 3 and adenovirus), she did not survive long enough to receive a bone marrow transplant. Newborn screening would not only have made the diagnosis at birth but would have led to measures to protect her from becoming infected before she could receive a transplant. Newborn screening would also reveal the true incidence of SCID and define the range of conditions characterized by severely impaired T-cell development. Until screening for SCID and other T-cell defects becomes available for all neonates (either by quantifying T-cell receptor excision circles in Guthrie spots or using other tests that quantify T cells), all pediatricians should know the normal range for ALCs according to age. Recognition of the characteristic lymphopenia of SCID can facilitate early diagnosis.

Distribution of Primary Immunodeficiency Diseases in the Turk Ethnic Group, Living in the Northwestern Iran

Primary immunodeficiency disorders (PID) are a heterogeneous group of disorders, characterized by an unusual increased susceptibility to various infections. In order to study the frequency of PID in Turk ethnic group of northwestern Iran, this study was performed. Fifty-nine PID patients (36 male and 23 female) with a mean age of 5.3 years (median: 3 years; range: <1 to 22 years) were diagnosed in a 5-year period. The estimated occurrence of PID is about 24 per 100,000 live births in this region. Combined T- and B-cell immunodeficiencies were the most common form of PID in this region, including severe combined immunodeficiency (32.2%), followed by ataxia-telangiectasia (22.0%) and common variable immunodeficiency (18.6%). Recurrent infections were found in almost all our patients, particularly in the respiratory and gastrointestinal systems. Fifteen patients died (25.4%) because of recurrent and severe infections. All dead patients belong to the group of combined T- and B-cell immunodeficiencies. Although PID was previously considered as a group of rare disorders, these is an increased trend in recognition of PID. The high incidence of severe combined immunodeficiency and ataxia-telangiectasia could be due to the genetic backgrounds in the Turk ethnic group.

Primary Immunodeficiency Diseases in Latin America: The Second Report of the LAGID Registry

This is the second report on the continuing efforts of LAGID to increase the recognition and registration of patients with primary immunodeficiency diseases in 12 Latin American countries: Argentina, Brazil, Chile, Colombia, Costa Rica, Honduras, Mexico, Panama, Paraguay, Peru, Uruguay, and Venezuela. This report reveals that from a total of 3321 patients registered, the most common form of primary immunodeficiency disease was predominantly antibody deficiency (53.2%) with IgA deficiency reported as the most frequent phenotype. This category was followed by 22.6% other well-defined ID syndromes, 9.5% combined T- and B-cell inmunodeficiency, 8.6% phagocytic disorders, 3.3% diseases of immune dysregulation, and 2.8% complement deficiencies. All countries that participated in the first publication in 1998 reported an increase in registered primary immunodeficiency cases, ranging between 10 and 80%. A comparison of the estimated minimal incidence of X-linked agammaglobulinemia, chronic granulomatous disease, and severe combined immunodeficiency between the first report and the present one shows an increase in the reporting of these diseases in all countries. In this report, the estimated minimal incidence of chronic granulomatous disease was between 0.72 and 1.26 cases per 100,000 births in Argentina, Chile, Costa Rica, and Uruguay and the incidence of severe combined immunodeficiency was 1.28 and 3.79 per 100,000 births in Chile and Costa Rica, respectively. However, these diseases are underreported in other participating countries. In addition to a better diagnosis of primary immunodeficiency diseases, more work on improving the registration of patients by each participating country and by countries that have not yet joined LAGID is still needed.

Development of Population-Based Newborn Screening for Severe Combined Immunodeficiency

Purpose of the Study. To evaluate analysis of T-cell development as a potential population-screening method for severe combined immunodeficiency (SCID). Study Population. Twenty-three infants with SCID, 2 patients without SCID, 245 randomly selected infants, and several healthy adults. Methods. DNA was extracted from dried blood spots on standard newborn screening (Guthrie) cards. The DNA was subjected to polymerase chain reaction (PCR) to amplify and quantitate the number of T-cell receptor excision circles (TRECs), a marker of T-cell development in the thymus. For comparison, the β-actin gene was also amplified by PCR. Results. None of the SCID patients’ blood spots contained detectable TRECs, whereas the infants without SCID had normal TRECs. Healthy adults had normal TRECs, and intentional depletion of T cells led to the disappearance of TRECs in simulated blood spots. Approximately 3% of randomly collected blood spots did not contain measurable TRECs but did contain β-actin. Conclusions. Measurement of TRECs by PCR can accurately identify infants with SCID. The relatively high percentage (3%) of screened spots having the SCID profile indicates the need for further refinement of the method before a larger population study. Reviewer Comments. Newborn screening for SCID is desirable because of the rapidly fatal nature of this disease and because of the good outcomes that may be obtained with the earliest possible diagnosis. The minimum estimate of the incidence of SCID is &amp;gt;1 per 100 000 births, comparable to other diseases that are already part of newborn screening programs. Almost all patients with SCID lack detectable TRECs. The ability to accurately measure them in dried blood spots represents a tremendous advance toward the possibility of effective newborn screening for this genetically very heterogeneous group of disorders. If the specificity of the analysis can be improved, this may soon be implemented in newborn screening programs.

High Incidence of Severe Combined Immune Deficiency in the Eastern Province of Saudi Arabia

Severe combined immunodeficiency (SCID) is a group of rare genetic disorders with an estimated incidence of 1 in 50,000 to 1 in 500,000 live births, invariably fatal in early infancy if not corrected. In the period 1990–2002 we diagnosed 18 cases of SCID in 11 Saudi Arab families at our hospital, which serves a population of 250,000 in the eastern province of Saudi Arabia. During the same period there were 90,555 live births. Of the 18 cases of SCID, 7 children survived, 6 after HLA identical fully matched bone marrow transplantation from siblings, 1 child with adenosine deaminase deficiency (ADA) surviving on ADA replacement. The other 11 patients died from serious infections. The incidence of SCID in our population is 19 per 100,000 live births, the highest incidence reported in the world. Most of our cases are autosomal recessive, and the product of consanguineous marriage. If we exclude the minor immunoglobulin (Ig)A and IgG subclass deficiencies, SCID represents 50% of all serious primary immunodeficiency in our pediatric population. (Pediatr Asthma Allergy Immunol 2006; 19[1]:14–18.)

GENE ENRICHMENT IN AN AMERICAN INDIAN POPULATION: AN EXCESS OF SEVERE COMBINED IMMUNODEFICIENCY DISEASE

A subgroup of Athabascan Indians in Arizona and New Mexico was found to have an unusually high incidence of severe combined immunodeficiency, probably due to founder effect. Closed genetic pressures have limited their histocompatibility-antigen heterogeneity, enabling 3 patients to be grafted, 2 of them across HLA-B locus barriers.