Severe Congenital Neutropenia Due To G6PC3 Deficiency Case Series of Five Patients and Literature Review

Glucose-6-phosphate catalytic subunit 3 (G6PC3) deficiency is characterized by severe congenital neutropenia with recurrent pyogenic infections, a prominent superficial venous pattern, and cardiovascular and urogenital malformations, caused by an alteration of glucose homeostasis, with increased endoplasmic reticulum stress and cell apoptosis. We describe five new cases from Mexico, and review 89 more patients reported in the past decade, to delineate the most frequent laboratory and genetic features, their treatment, and outcomes, and to expand the knowledge of syndromic and non-syndromic phenotypes in these patients.

Severe congenital neutropenia due to G6PC3 deficiency. Case series of five patients and literature review

Glucose-6-phosphate catalytic subunit 3 (G6PC3) deficiency is characterized by severe congenital neutropenia with recurrent pyogenic infections, a prominent superficial venous pattern, and cardiovascular and urogenital malformations, caused by an alteration of glucose homeostasis, with increased endoplasmic reticulum stress and cell apoptosis. We describe five new cases from Mexico, and review 89 more patients reported in the past decade, to delineate the most frequent laboratory and genetic features, their treatment, and outcomes, and to expand the knowledge of syndromic and non-syndromic phenotypes in these patients.

RecurrentC. difficilein a Patient with IgG Deficiency

IgG deficiency can predispose to recurrent pyogenic infections. The association of IgG deficiency withClostridium difficileinfection has been infrequently reported in the literature. We present a case of a middle-age woman with multiple hospitalizations for recurrentC. difficilein a short span of time which prompted consideration of a possible fecal transplant. On evaluation, she was found to have low total IgG, with subclass analysis revealing low IgG1 and IgG3. She was started on monthly infusions of immunoglobulins and one year after her last episode ofC. difficileshe has not had any recurrence. The role of immunoglobulin infusion in the treatment of recurrentC. difficileis controversial, with some studies revealing no clear evidence of benefit. Our case report suggests that the patients who have underlying IgG deficiency may benefit from immunoglobulin, as this can significantly reduce the incidence of recurrent infections and hence save the healthcare costs.

Serum Bactericidal Antibody Responses to Meningococcal Polysaccharide Vaccination as a Basis for Clinical Classification of Common Variable Immunodeficiency

ABSTRACT Common variable immunodeficiency (CVID) is a heterogeneous group of disorders characterized by hypogammaglobulinemia and increased susceptibility to recurrent pyogenic infections. This study was performed to subclassify CVID on the basis of the bactericidal antibody responses of patients to polysaccharide meningococcal vaccine. Twenty-five patients with CVID (18 male and 7 female) and 25 healthy volunteers received meningococcal polysaccharide vaccine A + C. Serum bactericidal antibody (SBA) titers were measured at baseline and after 3 weeks. Response was correlated with clinical and immunological manifestations of CVID. Twenty-four (96%) of the 25 normal controls had a protective SBA titer of ≥8 postvaccination, whereas only 16 (64%) of the 25 CVID patients had a protective titer (P value = 0.013). Among the patients with CVID who were nonresponders, there were significantly increased rates of bronchiectasis (P = 0.008), splenomegaly (P = 0.016), and autoimmunity (P = 0.034) in comparison with patients who had protective SBA titers. A reversed CD4/CD8 ratio was more common in the nonresponder group of patients (P = 0.053). We conclude that individuals with CVID who cannot produce protective postvaccination titers after receiving meningococcal polysaccharide vaccine are more likely to exhibit bronchiectasis, splenomegaly, and autoimmune diseases. Vaccination response may define subgroups of patients with CVID, enabling more effective monitoring and therapeutic strategies.

Corticosteroids in the Management of Cystitis Secondary to Chronic Granulomatous Disease

Chronic granulomatous disease refers to a group of inherited disorders characterized by a deficit in phagocytic-cell oxidative metabolism, resulting in recurrent pyogenic infections due to defective intracellular killing of microorganisms.1 Granulomas form in various organs or tissues, presumably in an attempt to "wall off" the infection, and these can be a major cause of morbidity when vital structures are obstructed or compromised. Cultures of the granulomas are usually negative, although antibiotics have been advocated in the treatment of this complication. Recently, three patients with chronic granulomatous disease-two with gastrointestinal and genitourinary involvement2 and one with pulmonary involvement3—were treated with corticosteroids, which resulted in an amelioration of symptoms.

Inherited Deficiency of the Third Component of Complement Associated with Recurrent Pyogenic Infections, Circulating Immune Complexes, and Vasculitis in a Dutch Family

A family is described in which 3/11 children showed a homozygous deficiency of C3, and both parents and six other children had subnormal levels of C3. The three children with selective C3 deficiency suffered repeatedly from bacterial infections, whereas the parents and the other siblings were clinically healthy. During infectious episodes the patients showed a maculopapular skin rash, and at such times immune complexes were present in the serum. Biopsy specimens of the skin lesions showed the picture of leukocytoclastic vasculitis.

Defective Polymorphonuclear Leukocyte Chemotaxis and Bactericidal Capacity in a Boy With Recurrent Pyogenic Infections

A 13-year-old boy with a history of recurrent pyogenic infections had abnormalities of polymorphonuclear leukocyte (PMN) function which probably accounted for his susceptibility to infection. PMN phagocytosis and nitroblue tetrazolium dye reduction were normal but glucose 14C oxidation was abnormally increased in resting cells. The patient's PMNs possessed decreased bactericidal activity against Staphylococcus aureus and Escherichia coli. Also documented were decreased PMN chemotactic activity and leukocyte accumulation in Rebuck skin windows. PMN random motility, PMN bone marrow reserve, PMN kinetics, lymphocyte blastogenesis, and delayed cutaneous hypersensitivity were normal. This patient represents another of the growing number of distinct granulocytopathies currently being recognized which may result in increased susceptibility to infection.