exudates and Immunologic-Deficiency-Syndromes

Primary immunodeficiency diseases refer to inborn errors of immunity (IEI) that affect the normal development and function of the immune system. The phenotypical and genetic heterogeneity of IEI have made their diagnosis challenging. Hence, whole-exome sequencing (WES) was employed in this pilot study to identify the genetic etiology of 30 pediatric patients clinically diagnosed with IEI. The potential causative variants identified by WES were validated using Sanger sequencing. Genetic diagnosis was attained in 46.7% (14 of 30) of the patients and categorized into autoinflammatory disorders (n = 3), diseases of immune dysregulation (n = 3), defects in intrinsic and innate immunity (n = 3), predominantly antibody deficiencies (n = 2), combined immunodeficiencies with associated and syndromic features (n = 2) and immunodeficiencies affecting cellular and humoral immunity (n = 1). Of the 15 genetic variants identified, two were novel variants. Genetic findings differed from the provisional clinical diagnoses in seven cases (50.0%). This study showed that WES enhances the capacity to diagnose IEI, allowing more patients to receive appropriate therapy and disease management.

Topics: Child; Child, Preschool; Exome Sequencing; Female; Genetic Diseases, Inborn; Humans; Immunity, Cellular; Immunity, Innate; Immunologic Deficiency Syndromes; Infant; Malaysia; Male; Pilot Projects

Topics: Anemia, Aplastic; Bone Marrow Transplantation; China; Cooperative Behavior; Family; Hematopoietic Stem Cell Transplantation; Hemoglobinopathies; Hong Kong; Humans; Immunologic Deficiency Syndromes; Leukemia; Lymphoma; Malaysia; Myelodysplastic Syndromes; Peripheral Blood Stem Cell Transplantation; Philippines; Singapore; Thailand; Tissue Donors; Transplantation, Autologous; Transplantation, Homologous

To determine the clinical and epidemiological characteristics of patients seen with primary immunodeficiencies referred at four Malaysian Hospitals between 1987 to 2007.. Patient data were retrospectively obtained from patient records and supplemented by information from a standardized questionnaires taken at the time of diagnosis from 4 participating hospitals. The completed data were transferred to document records kept by the first author. The diagnoses made were based on criteria set by WHO Scientific Committee 1986.. Fifty one (51) patients with completed records satisfied the criteria of primary immunodeficiencies based on WHO Scientific Committee 1986. Predominant Antibody deficiency (40.4%) is the commonest of the class of primary immunodeficiency (based on modified IUIS classification) followed by phagocytic defect (17.3%), combined immunodeficiencies (15.4%) and other cellular immunodeficiencies (11.5%). The commonest clinical presentation is pneumonia (54%) . A positive Family history with a close family relative afflicted was a strong pointer to diagnosis for PID (52.6%) Primary immnodeficiencies are seen in all the major ethnic groups of Malaysia, predominantly among Malays. As observed in other patient registries, diagnostic delay remains the major cause of morbidity and mortality.. Primary immunodeficiencies is relative rare but is an emerging disease in Malaysia. Creating awareness of the disease, may reveal more cases within the community. It is sufficient to be a health issue in Malaysia as in other developing countries in the future.

Topics: Delayed Diagnosis; Humans; Immunologic Deficiency Syndromes; Malaysia; Registries; Surveys and Questionnaires