RESUMEN
BACKGROUND: Mendelian susceptibility to mycobacterial disease (MSMD) is a rare primary immunodeficiency, caused by non-tuberculous mycobacteria or Bacillus Calmette-Guerin (BCG) vaccine and characterized by severe diseases in childhood. OBJECTIVE: In this study, we examined eight years followed-up 12 Turkish children with genetically proven MSMD and we tried to evaluate the survival rate with succesfull disease management, rate of consanguinity, molecular, cellular and clinical features of patients. In addition, we wanted to emphasize the importance of early diagnosis before administration of BCG vaccine in countries where this vaccine is routinely used. METHODS: Twelve patients diagnosed with molecular studies [IFNγR1 complete (n = 1), IFNγR2 partial (n = 3), IL12Rß1 (n = 6), NEMO (n = 1), STAT1 mutation (n = 1)] were included. RESULTS: Ten patients (83%) were born from consanguineous parents and frequency of family history for the primary immunodeficiency was 58% (n = 7). All the cases had been immunized with BCG vaccine (Mycobacterium bovis) due to lack of early diagnosis. Two patients had BCG-itis and four patients had "BCG-osis". Survival rate was 75% after successful disease management with antibiotics, anti-tuberculous agents and recombinant IFN-γ. CONCLUSIONS: It was concluded that MSMD must be differentiated from different forms of primary immunodeficiencies, so clinicians should be aware of MSMD especially in patients with BCG vaccine complications and non-tuberculous mycobacterial infection.
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Infecciones por Mycobacterium , Mycobacterium bovis , Humanos , Niño , Vacuna BCG/efectos adversos , Estudios de Seguimiento , Infecciones por Mycobacterium/genética , Mutación , Predisposición Genética a la EnfermedadRESUMEN
BACKGROUND: Lipopolysaccharide-responsive beige-like anchor protein (LRBA) deficiency and cytotoxic T-lymphocyte protein-4 (CTLA-4) insufficiency are recently described disorders that present with susceptibility to infections, autoimmunity, and lymphoproliferation. Clinical and immunological comparisons of the diseases with long-term follow-up have not been previously reported. We sought to compare the clinical and laboratory manifestations of both diseases and investigate the role of flow cytometry in predicting the genetic defect in patients with LRBA deficiency and CTLA-4 insufficiency. METHODS: Patients were evaluated clinically with laboratory assessments for lymphocyte subsets, T follicular helper cells (TFH ), LRBA expression, and expression of CD25, FOXP3, and CTLA4 in regulatory T cells (Tregs) at baseline and 16 h post-stimulation. RESULTS: LRBA-deficient patients (n = 29) showed significantly early age of symptom onset, higher rates of pneumonia, autoimmunity, chronic diarrhea, and failure to thrive compared to CTLA-4 insufficiency (n = 12). In total, 29 patients received abatacept with favorable responses and the overall survival probability was not different between transplanted versus non-transplanted patients in LRBA deficiency. Meanwhile, higher probability of survival was observed in CTLA-4-insufficient patients (p = 0.04). The T-cell subsets showed more deviation to memory cells in CTLA-4-insufficiency, accompanied by low percentages of Treg and dysregulated cTFH cells response in both diseases. Cumulative numbers of autoimmunities positively correlated with cTFH frequencies. Baseline CTLA-4 expression was significantly diminished in LRBA deficiency and CTLA-4 insufficiency, but significant induction in CTLA-4 was observed after short-term T-cell stimulation in LRBA deficiency and controls, while this elevation was less in CTLA-4 insufficiency, allowing to differentiate this disease from LRBA deficiency with high sensitivity (87.5%) and specificity (90%). CONCLUSION: This cohort provided detailed clinical and laboratory comparisons for LRBA deficiency and CTLA-4 insufficiency. The flow cytometric approach is useful in predicting the defective gene; thus, targeted sequencing can be conducted to provide rapid diagnosis and treatment for these diseases impacting the CTLA-4 pathway.
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Proteínas Adaptadoras Transductoras de Señales , Lipopolisacáridos , Abatacept/metabolismo , Abatacept/uso terapéutico , Proteínas Adaptadoras Transductoras de Señales/metabolismo , Antígeno CTLA-4/genética , Antígeno CTLA-4/metabolismo , Factores de Transcripción Forkhead/metabolismo , HumanosRESUMEN
INTRODUCTION: Food protein-induced enterocolitis syndrome (FPIES) is a rare non-IgE, cell-mediated food allergy disorder. We aimed to report the demographic characteristics, clinical features, and management of pediatric patients with FPIES. METHODS: This retrospective study included all children diagnosed with FPIES at the pediatric allergy departments of the participating twelve study centers from January 2015 to November 2020. RESULTS: A total of 73 patients (39 males, 53.4%) with a male/female ratio of 1.1 were included in the study. The median (interquartile ranges) age at symptom onset was 6 months (0.5-168, 4-9.5). The most frequent offending foods were cow's milk, egg's yolk, fish, and egg's white, identified in 38.4% (n = 28), 32.9% (n = 24), 21.9% (n = 16) and 20.5% (n = 15) of the patients, respectively. The total number of reported FPIES episodes was 290 (3.9 episodes per child). Oral food challenge (OFC) was performed in 54.8% (n = 40) of the patients, and tolerance was detected in 17 OFCs (42.5%) at a median age of 15 months (range 8-132 months). CONCLUSION: FPIES is a non-IgE-mediated food hypersensitivity that commonly affects infants and is often misdiagnosed. The pathophysiology of the disease remains unclear and the low awareness of FPIES among physicians and parents highlights the need for more education.
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Enterocolitis , Hipersensibilidad a los Alimentos , Alérgenos , Animales , Bovinos , Proteínas en la Dieta/efectos adversos , Enterocolitis/diagnóstico , Enterocolitis/epidemiología , Enterocolitis/etiología , Femenino , Hipersensibilidad a los Alimentos/diagnóstico , Hipersensibilidad a los Alimentos/epidemiología , Humanos , Tolerancia Inmunológica , Masculino , Estudios RetrospectivosRESUMEN
INTRODUCTION AND OBJECTIVES: The purpose of this study was to evaluate patients diagnosed with 22q11.2 deletion syndrome and determine the clues directing to diagnosis and evaluation of immunological findings for excellent management of the disease. MATERIAL AND METHODS: Thirty-three pediatric patients with 22q11.2 deletion syndrome diagnosed between 1998 and 2019 at Pediatric Immunology Division of Ege University Faculty of Medicine and SBU Izmir Dr Behcet Uz Children's Education and Research Hospital were evaluated. RESULTS: This study includes the largest case series reported from Turkey. Congenital cardiac anomalies were the most common pathology associated with the syndrome (90.9%). Hypocalcemic symptoms were observed in 13 patients (40%). Twenty-two of the 33 (66.6%) patients were diagnosed before two years of age. Autoimmune diseases, dysmorphic facial findings, recurrent infections, growth retardation, and speech impairment were other clues for diagnosis in older patients. Clinical spectrum and immunological abnormalities of this syndrome are quite variable. All T-cell subset counts were less than 5th percentile below median by age in one patient (3%) and 10 patients had normal all T-cell subset counts (30.3%). Overall, 69.6% of the patients had normal IgG, IgA, and IgM levels and two patients had panhypogammaglobulinemia. Recurrent infections were revealed in 75.7% of the patients during follow-up. CONCLUSIONS: Presence of cardiac anomaly is more helpful in the diagnosis, especially under two years of age. Patients with immunologically high or standard risk did not show any difference in terms of numbers and severity of infections and autoimmunity.
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Síndrome de DiGeorge/diagnóstico , Síndrome de DiGeorge/terapia , Anomalías Múltiples/diagnóstico , Anomalías Múltiples/inmunología , Anomalías Múltiples/terapia , Niño , Preescolar , Síndrome de DiGeorge/inmunología , Manejo de la Enfermedad , Femenino , Cardiopatías Congénitas/diagnóstico , Cardiopatías Congénitas/inmunología , Cardiopatías Congénitas/terapia , Humanos , Hipocalcemia/diagnóstico , Hipocalcemia/inmunología , Hipocalcemia/terapia , Isotipos de Inmunoglobulinas/sangre , Lactante , Recién Nacido , Subgrupos Linfocitarios/citología , Masculino , TurquíaRESUMEN
Objectives Transcobalamin II (TC) is an essential plasma protein for the absorption, transportation, and cellular uptake of cobalamin. TC deficiency presents in the first year of life with failure to thrive, hypotonia, lethargy, diarrhea, pallor, mucosal ulceration, anemia, pancytopenia, and agammaglobulinemia. Herein, we present TC deficiency diagnosed in two cases (twin siblings) with a novel variant in the TCN2 gene. Case presentation 4-month-old twins were admitted with fever, respiratory distress, vomiting, diarrhea, and failure to thrive. Physical examination findings revealed developmental delay and hypotonia with no head control, and laboratory findings were severe anemia, neutropenia, and hypogammaglobulinemia. Despite normal vitamin B12 and folate levels, homocysteine and urine methylmalonic acid levels were elevated in both patients. Bone marrow examinations revealed hypocellular bone marrow in both cases. The patients had novel pathogenic homozygous c.241C>T (p.Gln81Ter) variant in the TCN2 gene. In both cases, with intramuscular hydroxycobalamin therapy, laboratory parameters improved, and a successful clinical response was achieved. Conclusions In infants with pancytopenia, growth retardation, gastrointestinal manifestations, and immunodeficiency, the inborn error of cobalamin metabolism should be kept in mind. Early diagnosis and treatment are crucial for better clinical outcomes. What is new? In literature, to date, less than 50 cases with TC deficiency were identified. In this report, we presented twins with TCN2 gene mutation. Both patients emphasized that early and aggressive treatment is crucial for achieving optimal outcomes. In this report, we identified a novel variation in TCN2 gene.