Heterogeneity in RAG1 and RAG2 deficiency: 35 cases from a single-centre.

Recombination activating genes (RAG)1 and RAG2 deficiency leads to combined T/B-cell deficiency with varying clinical presentations. This study aimed to define the clinical/laboratory spectrum of RAG1 and RAG2 deficiency. We retrospectively reviewed the clinical/laboratory data of 35 patients, grouped them as severe combined immunodeficiency (SCID), Omenn syndrome (OS), and delayed-onset combined immunodeficiency (CID) and reported nine novel mutations. The male/female ratio was 23/12. Median age of clinical manifestations was 1 months (mo) (0.5-2), 2 mo (1.25-5), and 14 mo (3.63-27), age at diagnosis was 4 mo (3-6), 4.5 mo (2.5-9.75), and 27 mo (14.5-70) in SCID (n = 25; 71.4%), OS (n = 5; 14.3%), and CID (n = 5; 14.3%) patients, respectively. Common clinical manifestations were recurrent sinopulmonary infections 82.9%, oral moniliasis 62.9%, diarrhea 51.4%, and eczema/dermatitis 42.9%. Autoimmune features were present in 31.4% of the patients; 80% were in CID patients. Lymphopenia was present in 92% of SCID, 80% of OS, and 80% of CID patients. All SCID and CID patients had low T (CD3, CD4, and CD8), low B, and increased NK cell numbers. Twenty-eight patients underwent hematopoietic stem cell transplantation (HSCT), whereas seven patients died before HSCT. Median age at HSCT was 7 mo (4-13.5). Survival differed in groups; maximum in SCID patients who had an HLA-matched family donor, minimum in OS. Totally 19 (54.3%) patients survived. Early molecular genetic studies will give both individualized therapy options, and a survival advantage because of timely diagnosis and treatment. Further improvement in therapeutic outcomes will be possible if clinicians gain time for HSCT.

Long Term Follow-Up of the Patients with Severe Combined Immunodeficiency After Hematopoietic Stem Cell Transplantation: A Single-Center Study.

BACKGROUND: We aimed to evaluate hematopoietic stem cell transplantation (HSCT) related outcomes of patients with severe combined immunodeficiency (SCID). METHODS: We retrospectively collected data from SCID patients who were diagnosed, followed up and survived at least 2 years after HSCT. RESULTS: Forty four SCID patients were included in the study. Median age of HSCT and follow-up period after HSCT were 7.1 months and 8.7 years, respectively. Human leukocyte antigen (HLA) identical donors were used in 77.3% (n = 34) of the patients (23 siblings, six fathers, two mothers, three extended family donors), HLA 1-2 mismatched family donors in 11.3% (n = 5), and haploidentical family donors in 11.3% (n = 5). CD3 and CD19 counts were normal in more than 90% and in 45.4% at last follow-up, respectively. Intravenous immunoglobulin (IVIG) could be stopped in 72.7% (n = 32) after HSCT. B+ SCID patients had better CD19 counts than B- (p < .001). T cell numbers, lymphocyte proliferation, IVIG need, immunoglobulin levels, antibody responses did not differ among B- and B+ immunophenotypes. Acute graft-versus-host disease (GVHD) was less in bone marrow transplanted patients (19.4%) than peripheral stem cell (58.3%) transplanted ones (p = .024). There was no correlation between age at transplantation and immune reconstitution. At the last follow-up, 70.2% and 78.3% of the patients had body weight and height above 3rd percentile, respectively. CONCLUSION: The immune reconstitution and the growth were normal in the majority of SCID patients after HSCT. It may be rational to use bone marrow instead of peripheral stem cell, as acute GVHD was less in bone marrow transplanted patients.

Infectious diseases, autoimmunity and midline defect in a patient with a novel bi-allelic mutation in IL12RB1 gene.

Clinical disease caused by weakly pathogenic mycobacterial species, which is known as Mendelian susceptibility to mycobacterial disease (MSMD), is a rare entity. IFN-γ and IL-17 production are defective due to insufficient response to IL-2 and IL-23 in IL-12Rß1 deficiency; so this also causes tendency to intracellular microorganisms and candidal diseases. Here, we present a patient who suffers IL-12Rß1 deficiency caused by a novel bi-allelic mutation with recurrent salmonellosis, mycobacterial, fungal infections and remained asymptomatic during 13 months of follow-up after hIFN-γ treatment. In addition she had hemolytic anemia and midline defects like cleft lip and palate which have not been reported in a patient with MSMD in the literature prior to this case report. In conclusion, diagnosis of MSMD should be kept in mind in patients with recurrent salmonellosis, mycobacterial and fungal infections especially in countries with a high consanguinity rate.

Gingivitis and Very High IgE Level in a Chronic Granulomatous Disease Patient with Unusual Presentation: A Case Report.

Chronic granulomatous disease (CGD) is a rare primary immunodeficiency disease characterized by recurrent bacterial and fungal infections and is due to impaired function of superoxide-producing nicotinamide adenine dinucleotide phosphate oxidase. Patients may have elevated serum IgE levels mainly because of a high incidence of sensitization to Aspergillus species. In addition to a predisposition to infections, patients with CGD might have hyperinflammation presenting itself as chronic inflammatory lesions involving gastrointestinal mucosa, skin, lungs, eyes, and brain. Here, we present a case that mainly presented with chronic gingivitis and very high serum IgE levels and had been referred to our hospital with a probable diagnosis of hyper-IgE syndrome, another congenital immunodeficiency that is also characterized by increased susceptibility to bacterial or fungal infections and very high serum IgE levels. Detailed history of the patient revealed recurrent upper and lower respiratory tract and skin infections. He was diagnosed as having CGD by documenting defective phagocyte superoxide production and the diagnosis was then confirmed by mutation analysis. Family screening revealed that a younger brother was also affected. CGD should be considered in the differential diagnosis of patients with recurrent infections, chronic inflammatory lesions, and high serum IgE levels. These cases emphasize the importance of detailed history taking for diagnosis and family screening for identification of other affected members.

Clinical features of chronic granulomatous disease: a series of 26 patients from a single center.

Chronic granulomatous disease is a genetically determined immunodeficiency disorder affecting phagocytic cells rendering them unable to kill certain bacteria and fungi. The present study is a single-center retrospective study that aimed to document the clinical course of 26 children, with a median age of 2.5 years, from 21 families diagnosed as chronic granulomatous disease from 1989-2008. A median delay of 39 months was observed between the onset of infections and age at diagnosis. Pneumonia was the most common initial manifestation of the disease followed by lymphadenitis, skin abscess and diarrhea. An AR inheritance was predominant in the study group. All patients received antibacterial and antifungal prophylaxis, resulting in a marked decrease in the incidence of infections. Overall mortality was 19.2%. These results showed that all features in our group (clinical, progression and outcome) were similar to the literature except for the predominance of autosomal recessive form.

Mild clinical phenotype and subtle radiographic findings in an infant with cartilage-hair hypoplasia.

Cartilage-hair hypoplasia (CHH) is one of the well-known immuno-osseous dysplasias (IOD), which are a combination of skeletal dysplasia and immunodeficiency. It is characterized by disproportionate short stature, fine sparse hair, ligamentous laxity, hematological abnormalities with anemia, a predisposition to malignant tumors, and recurrent infections usually due to cellular and/or humoral immunodeficiency. However, there is a significant overlap of clinical findings among the other IODS such as Schimke's IOD. Here, we present a case of CHH with mild skeletal changes and immunological findings associated with recurrent otitis media, neutropenia, and lymphopenia. With this report, we once more emphasize the difficulty in assessing young individuals with CHH presenting with mild ectodermal findings and subtle radiographic changes.