Enteroviral Infection in a Patient with BLNK Adaptor Protein Deficiency.

B-cell linker (BLNK) protein is a non-redundant adaptor molecule in the signaling pathway activated by (pre) B-cell antigen receptor signals. We present two siblings with a homozygous deleterious frameshift mutation in BLNK, resulting in a block of B cell development in the bone marrow at the preB1 to preB2 stage, absence of circulating B cells and agammaglobulinemia. This is the first description of an enteroviral infection associated arthritis and dermatitis in a patient with BLNK deficiency.

A novel de novo PSTPIP1 mutation in a boy with pyogenic arthritis, pyoderma gangrenosum, acne (PAPA) syndrome.

Autoinflammatory disorders are a group of Mendelian disorders characterized by seemingly unprovoked inflammatory bouts without high-titer autoantibodies or antigen-specific T-cells and are probably due to defects in the innate immunity. We here report on a 4-year-old Arabic boy with the clinical presentation of an autoinflammatory disorder, namely Pyogenic Arthritis, Pyoderma Gangrenosum and Acne (PAPA) syndrome. The presentation includes abscess formation after immunization and recurrent mono-articular acute arthritis in various joints that responded favourably to systemic glucocorticosteroids, albeit without acne or pyoderma gangrenosum. The mutation analysis of the boy identified a novel de novo mutation in PSTPIP1, the gene responsible for PAPA syndrome. We recommend that the diagnosis of PAPA syndrome should be entertained in the differential diagnosis of patients with recurrent sterile pyogenic arthritis prior to the development of pyoderma gangrenosum or acne in order to initiate a timely management of the disorder.

Primary antibody deficiencies at Queen Rania Children Hospital in Jordan: single center experience.

BACKGROUND: Primary antibody deficiency, the most common primary immunodeficiency disorder, represents a heterogeneous spectrum of conditions caused by a defect in any critical stage of B cell development and is characterized by impaired production of normal amounts of antigen-specific antibodies. OBJECTIVE: This retrospective study aimed at description and analysis of demographic, clinical, immunological features and complications of subjects diagnosed with primary antibody deficiency at a referral center in Jordan. METHODS: The medical records of pediatric patients who were diagnosed as primary antibody deficiency (PAD) during the period from January 2006 to June 2013 were reviewed. Patients were diagnosed as PADs based on the Pan-American Group for Immunodeficiency (PAGID) and the European Society for Immunodeficiency (ESID) diagnostic criteria. RESULTS: A total number of 53 patients with PAD were identified; 37(70%) males and 16(30%) females, 16(30%) patients with congenital agammaglobulinemia, 16(30%) patients with common variable immunodeficiency, 4(7.5%) patients with IgG subclass deficiency, 10(19%) cases with transient hypogammaglobulinemia of infancy and 7(13.5%) patients as undefined PAD. The most common infection among patients was pneumonia (62%); followed by suppurative otitis media in 49% of patients. Cytopenia was the most noted autoimmune association and was found at prevalence of 22 %, other autoimmune associations (17%) including inflammatory arthritis, discoid lupus, inflammatory bowel disease, vasculitis and celiac disease. The prevalence of long-term complications was 58%, the most frequent ones were; stunted growth in 13%, bronchiectasis and lymphoproliferation in 11% for each. CONCLUSIONS: Our results indicated that congenital agammaglobulinemia and common variable immunodeficiency are the most frequent primary antibody deficiency in our patients. The awareness of families, general population as well as primary health physicians is crucial in the establishment of early diagnosis and prompt commencement of appropriate therapy for PADs.

Mismatched related hematopoietic stem cell transplantation in primary immunodeficiency.

Hematopoietic stem cell transplantation (HSCT) is the definitive therapy for a variety of primary immunodeficiency syndromes (PIDs). However, no more than 30% of the patients will have a human leukocyte antigen (HLA)-identical sibling. We retrospectively analyzed our results of ten patients with PID; severe combined immunodeficiency (SCID) (n = 7), hyper IgM (HIgM) (n = 1) and combined immunodeficiency (CID) (n = 2), who lacked a fully matched donor and underwent mismatched related HSCT during the period from 2008 to 2010. The median age at the time of transplantation ranged between 3 and 84 months (median 6.5 months). Peripheral blood stem cells (PBSC) were used in all HSCTs. The mean value of the peripheral CD34+ cells infused was 9.19 × 10 (6) /kg recipient weight. Patients received different conditioning protocols. All patients received anti graft versus host disease (GVHD) prophylaxis and all were engrafted. Mixed chimerism (5-55%) was noticed. GVHD was observed in 50% of the patients. Post-transplant follow-up ranged from 3 weeks to 36 months (median 15 months). Five patients are still alive while one patient developed engraftment syndrome followed by graft slippage for which a second transplant with CD34+ stem cells 5.8 × 10 (6) /kg recipient's weight was infused. The others died from sepsis and transplant-related complications. Immune reconstitution was noticed in four patients. In conclusion, HLA-haploidentical stem cell transplantation may be feasible, with appropriate GVHD prophylaxis, for patients with PID who lack a fully matched donor.

Orofacial findings in chronic granulomatous disease: report of twelve patients and review of the literature.

BACKGROUND: Chronic granulomatous disease is an extremely rare primary immunodeficiency syndrome that can be associated with various oral complications. This can affect high number of patients. However, data on oral complications is sparse. Here we will review the literature and describe the orofacial findings in 12 patients. FINDINGS: The age range was 5-31 years. Oral findings were variable, and reflected a low level of oral hygiene. They included periodontitis, rampant caries, gingivitis, aphthous-like ulcers, and geographic tongue. One patient had white patches on the buccal mucosa similar to lichen planus. Another patient had a nodular dorsum of the tongue associated with fissured and geographic tongue. Biopsies from the latter two lesions revealed chronic non-specific mucositis. Panoramic radiographs showed extensive periodontitis in one patient and periapical lesions in another patient. CONCLUSION: Patients with chronic granulomatous disease may develop oral lesions reflecting susceptibility to infections and inflammation. It is also possible that social and genetic factors may influence the development of this complication. Therefore, oral hygiene must be kept at an optimum level to prevent infections that can be difficult to manage.

First report of clinical, functional, and molecular investigation of chronic granulomatous disease in nine Jordanian families.

INTRODUCTION: Chronic granulomatous disease is a rare inherited immunodeficiency syndrome caused by mutations in four genes encoding essential nicotinamide adenine dinucleotide phosphate (NADPH) oxidase complex components. MATERIAL AND METHODS: Clinical, functional, and molecular investigations were conducted in 15 Jordanian CGD patients from nine families. RESULTS AND DISCUSSION: Fourteen patients were children of consanguineous parents and suffered from autosomal recessive (AR) CGD forms with mutations in the CYBA, NCF1, and NCF2 genes encoding p22phox, p47phox, and p67phox proteins, except for one patient in whom the mutation's location was not found. One patient had an extremely rare X(+)CGD subtype resulting from a novel missense mutation (G1234C) in exon 10 of CYBB. We found a genetic heterogeneity in the Jordanian families with a high frequency of rare ARCGD, probably because consanguineous marriages are common in Jordan. No clear correlation between the severity of the clinical symptoms and the CGD types could be established.

Periodontal manifestation of leukocyte adhesion deficiency type I.

BACKGROUND: Leukocyte adhesion deficiency type I (LAD-I) is an autosomal recessive immunodeficiency disorder characterized by defects in the integrin receptors of white blood cells that lead to impaired adhesion and chemotaxis. Affected patients are susceptible to recurrent bacterial and fungal infections, impaired pus formation, delayed wound healing, and periodontitis. METHODS: A case of generalized advanced periodontal destruction of the permanent and deciduous dentition in a young Jordanian girl with a severe phenotype of LAD-I is presented in this report. The medical diagnosis was made based on the characteristic clinical and laboratory findings, in particular the total absence of CD18, CD11b, and CD11c as determined by flow cytometry sorting. RESULTS: Periodontal findings in this patient include the early onset of the disease, which affected the primary teeth and permanent dentitions, the intense redness and inflammation of the gingiva, and the rapid periodontal destruction that seems refractory to conventional non-surgical periodontal therapy. CONCLUSION: This report emphasizes the importance of the differential diagnosis of severe immunodeficiency disorders in children and adolescents and mandates the importance of combined care by medical and dental practitioners to prevent tooth loss and control oral infection.