Mutational screening of WASP gene in patients with Wiskott-Aldrich syndrome

The Wiskott-Aldrich syndrome (WAS) is a rare X-linked recessive immunodeficiency disorder characterized by thrombocytopenia and small-sized platelets, eczema, recurrent bacterial and viral infections, higher incidence of autoimmunity and an increased risk of malignancies. WAS occurs due to the mutation or loss of Wiskott-Aldrich Syndrome Protein (WASP) gene located on Xp11.22 – p11.23 of the short arm of the X chromosome. The absence of functional WASP leads to severe clinical symptoms that results in the deaths of patients if they are not diagnosed and treated early. The objective of the study was to identify mutations in the WASP gene of families with children diagnosed with WAS.The whole coding sequence and the intron-exon flanking regions of the WASP were sequenced by Sanger method. Two cases of children who has WAS were found tocarrymutations in the WASP gene. A c.702insAC mutation leadeda frameshift at position of codon 236 and terminated the protein at the position of codon 262 was identified in patient WA007 and a c.91G>A mutation that transformed glutamic acid to lysineat codon 31 was determined in patient WA010.This study provides a data set and screening of mutations in theWASP gene inVietnamese patientsto further identify the genetic causes and contribute to the clinical management and genetic counseling for the affected families.

A chronic granulomatous disease masked by tuberculosis in a 2-year, 2-month old child: a case report

Chronic granulomatous disorder is a rare primary immunodeficiency disorder with phagocytic defect resulting in recurrent bacterial infections. Here we report a 2-year 2-month old male child, who presented with recurrent lymphadenitis and recurrent pneumonia since early infancy. In recent episode he presented with right cervical lymphadenopathy. Biopsy of lymph node revealed confluent necrotizing epithelioid cell granulomas and occasional giant cells but without evidence of tuberculosis and atypical organisms. His dihydrorhodamine 1,2,3 assay (DHR) was positive. Later he responded to prolonged parenteral antibiotics and discharged on itraconazole and trimethoprim-sulhamethaxazole prophylaxis. Here we are going to report a rare case of chronic granulomatous disease whose diagnosis was masked by tuberculosis

Wiskott-Aldrich Syndrome

The Wiskott-Aldrich syndrome (WAS) could be a rare X-linked primary immunodeficiency disorder characterized by recurrent infections, eczema, and bleeding following thrombocytopenia. Despite the rarity of this syndrome, today our understanding of the cellular and molecular basis of the pathogenesis of this disease has increased and it’s well established that this disorder encompasses a wide range of clinical disorders including immunodeficiency, atopy, autoimmunity, and cancer. Wiskott–Aldrich Syndrome protein (WASP) mutations are located throughout the gene and inhibit or regulate the conventional function of WASP. Thus classic WAS occurs when WASP is absent, X-linked thrombocytopenia when mutated WASP is expressed, and X-linked neutropenia when missense mutations occur within the Cdc42-binding site. Developments within the use of diagnostic tools, supportive care, and advances in allogeneic hematopoietic cell transplantation have remarkably reduced the mortality related to this disorder. Besides, gene therapy has provided optimistic perspectives on the treatment approaches of those patients.

Second Report of Chronic Granulomatous Disease in Jordan: Clinical and Genetic Description of 31 Patients From 21 Different Families, Including Families From Lybia and Iraq

Chronic granulomatous Disease (CGD) is a rare innate immunodeficiency disorder caused by mutations in one of the six genes (CYBA, CYBB, NCF1, NCF2, NCF4, and CYBC1/EROS) encoding the superoxide-producing nicotinamide adenine dinucleotide phosphate (NADPH)—oxidase complex in phagocytes. In the Western population, the most prevalent form of CGD (about two-thirds of all cases) is the X-linked form (X-CGD) caused by mutations in CYBB. The autosomal recessive forms (AR-CGD), due to mutations in the other genes, collectively account for the remaining one-third of CGD cases. We investigated the clinical and molecular features of 22 Jordanian, 7 Libyan, and 2 Iraqi CGD patients from 21 different families. In addition, 11 sibling patients from these families were suspected to have been died from CGD as suggested by their familial and clinical history. All patients except 9 were children of consanguineous parents. Most of the patients suffered from AR-CGD, with mutations in CYBA, NCF1, and NCF2, encoding p22phox, p47phox, and p67phox proteins, respectively. AR-CGD was the most frequent form, in Jordan probably because consanguineous marriages are common in this country. Only one patient from non-consanguineous parents suffered from an X910 CGD subtype (0 indicates no protein expression). AR670 CGD and AR220 CGD appeared to be the most frequently found sub-types but also the most severe clinical forms compared to AR470 CGD. As a geographical clustering of 11 patients from eight Jordanian families exhibited the c.1171_1175delAAGCT mutation in NCF2, segregation analysis with nine polymorphic markers overlapping NCF2 indicates that a common ancestor has arisen ~1,075 years ago.

Common variable immunodeficiency disorder: a clinical case

Primary immunodeficiency is a rare congenital pathology associated with failure of immune system, manifested by disturbances of its functions. These defects lead to increased susceptibility of patients to various infectious agents, as well as the development of autoimmune, malignant and other diseases. Primary immunodeficiency is classified as a rare disease, which was previously associated with a poor prognosis with a high risk of mortality in childhood. To date, the emergence of highly effective treatment methods has changed the course and prognosis of these diseases. Clinicians of various specialties increasingly meet with this pathology in everyday practice, including adult age cohorts. In this regard, early diagnosis of primary immunodeficiency in adults becomes relevant, being associated with choosing optimal therapy, prevention of severe internal organ damage, determination of management strategy for the patient, as well as the need to identify inherited disorders and provide information to the patient’s family. Delayed verification of the diagnosis may cause disability of the patient and development of irreversible, often fatal complications. This article presents our own clinical case with a newly diagnosed clinical condition: Common variable immunodeficiency disorder (CVID), the most common form of primary immunodeficiency in adults. The symptoms of common variable immunodeficiency disorder appear in these patients in adulthood, but a high-quality collected history of the disease will allow you to trace symptoms in the patients even since early childhood. There is a common gap for several years between the onset of the disease and clinical diagnosis, since erroneous diagnosis is often made due to non-specific clinical symptoms that resemble other, more frequent diseases. The prognosis of patients with CVID depends on several factors: frequency of infections, structural disorders in the lungs, the occurrence of autoimmune diseases and the success of infection prevention. Thus, a variety of clinical forms of primary immunodeficiency, lack of awareness of doctors about this pathology, complexity of immunological examination in the general medical network lead to the fact that CVID is not diagnosed for long terms, and patients do not receive the necessary pathogenetic therapy. There is a need for drawing attention of doctors of various disciplines to the fact that the recurrent inflammatory processes of various localization, which are difficult to respond to adequate traditional therapy, may be caused by changes in the immune system, including congenital, genetically determined immunodeficiency.

Turning walking pneumonia into recurrent abscesses: a curious case of CVID and review of the literature

Background: common variable immunodeficiency (CVID) is a primary immunodeficiency disorder associated with a broad symptom presentation that is still being characterized. We report a rare case of recurrent mycoplasma skin abscesses in a patient with a history of autoimmune disorders and prolonged mycoplasma pneumonia who was diagnosed with CVID.Case presentation: a 34-year-old woman presented with a history of recurrent abscesses previously confirmed positive for Mycoplasma pneumoniae. Her past medical history of recurrent mycoplasma abscesses, prolonged mycoplasma pneumonia, and autoimmune disorders (mixed connective tissue disease and immune thrombocytopenia) raised suspicion of CVID. Workup included negative anti-mycoplasma antibody titers, hypogammaglobulinemia, and negative anti-pneumococcal antibody titers despite prior vaccination, solidifying the diagnosis of CVID. The patient was discharged on antibiotic and intravenous immunoglobulin therapy with improvement and now follows allergy and immunology long-term for treatment.Conclusions: her diagnostic history underscores the importance of considering the various criteria of CVID for diagnosis, and her unique presentation of M. pneumoniae skin abscesses highlights the broad sequelae patients with CVID can manifest.

Common variable immunodeficiency disorder associated with bronchiectasis: a case report

Common variable immunodeficiency disorder (CVID) is the commonest type of primary immunodeficiency disorders (PIDs) characterized by hypogammaglobulinemia, defective specific antibody production and increased susceptibility of recurrent infections. Autoimmunity, neoplasm and lymphoproliferative disorders are usually associated with CVID. In most cases, the cause is unknown, but multiple gene mutations (10%) may be associated with CVID. Here, we report an eight years old girl with CVID presented with recurrent infections, growth failure, generalized lymphadenopathy and hepatosplenomegaly. Chest examination and radiological findings of this girl were consistent with bronchiectasis. Lack of awareness among health care providers is the reason for delayed diagnosis of several years for this girl. Therefore, it is essential to raise awareness regarding PID patients among the physicians to improve the quality of life.