X-linked agammaglobulinemia diagnosed late in life: case report and review of the literature

Sigmon, Justin R.; Kasasbeh, Ehab; Krishnaswamy, Guha

doi:10.1186/1476-7961-6-5

Cited by 36 publications

(22 citation statements)

References 14 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…As an example, X-linked agammaglobulinemia, a disorder leading to profound loss of B cells, may present atypically or later in life [33,73,95,96,97,98,99,100,101,102,103,104,105,106,107] while CD40 ligand deficiency may present with deceptively unimpressive IgM levels [29]. Similarly, X-linked lymphoproliferative disorders may mimic CVID in men [108,109,110,111].…”

Section: Monogenic Disorders Mimicking Cvidmentioning

confidence: 99%

Common Variable Immunodeficiency: Etiological and Treatment Issues

Deane

Selmi

Naguwa

et al. 2009

Int Arch Allergy Immunol

View full text Add to dashboard Cite

One of the great advances in clinical medicine was the recognition of the pleomorphism of the immune response and the multiple afferent and efferent limbs of antigen processing and responsiveness. A significant contribution to this understanding was derived from studies of human immunodeficiency states, including both inherited and acquired syndromes. Amongst these syndromes, one of the most common, and least understood, is common variable immune deficiency (CVID). CVID is a syndrome that leads to a reduction in serum immunoglobulins and complications including recurrent infections. Management includes immunoglobulin replacement therapy; however, patients with CVID are at risk for complications of exogenous immunoglobulin administration as well as CVID-associated diseases such as autoimmune processes and malignancies. To assess the current state of knowledge in the field, we performed a literature review of a total of 753 publications covering the period of 1968 until 2008. From this list, 189 publications were selected for discussion. In this review, we demonstrate that while the molecular basis of CVID in many cases remains incompletely understood, significant strides have been made and it is now clear that there is involvement of several pathways of immune activation, with contributions from both T and B cells. Furthermore, despite the current gaps in our knowledge of the molecular pathogenesis of the syndrome, there have been dramatic advances in management that have led to improved survival and significantly reduced morbidity in affected patients.

show abstract

Section: Monogenic Disorders Mimicking Cvidmentioning

confidence: 99%

Common Variable Immunodeficiency: Etiological and Treatment Issues

Deane

Selmi

Naguwa

et al. 2009

Int Arch Allergy Immunol

View full text Add to dashboard Cite

show abstract

“…However, unlike XLA, B-cell numbers are substantially decreased in only about 10% of cases of CVID, and, even in these cases, the numbers of peripheral blood B cells are substantially higher than is observed in XLA. In males with XLA diagnosed in adulthood, many had IgG levels that were only moderately depressed or even normal [40], which may account for the delay in presentation, but, even in cases of relatively high immunoglobulin levels, the number of peripheral B cells was clearly markedly depressed [37,41,42]. Minimal hypomorphic Btk mutations are likely clinically silent, as these have only a subtle impact on peripheral B-cell number [43].…”

Section: Genetics Of Primary Immunodeficiency Disordersmentioning

confidence: 99%

Adult-onset presentations of genetic immunodeficiencies: genes can throw slow curves

Nelson

Lewis

2010

Current Opinion in Infectious Diseases

View full text Add to dashboard Cite

Purpose of Review The molecular and genetic mechanisms behind adult presentations of primary immunodeficiency diseases are examined, with particular emphasis on cases where this was heralded by severe, recurrent or opportunistic infection. Recent Findings A detailed analysis over the last two decades of the relationship between genotype and clinical phenotype for a number of genetic immunodeficiencies has revealed multiple mechanisms that can account for the delayed presentation of genetic disorders that typically present in childhood, including hypomorphic gene mutations and X-linked gene mutations with age-related skewing in random X-chromosome inactivation. Adult-onset presentations of chronic granulomatous disease, X-linked agammaglobulinemia, interleukin-12/T helper 1/interferon-gamma and interleukin-23/T helper 17/interleukin-17 pathway defects, and X-linked lymphoproliferative disorder are used to illustrate these mechanisms. Finally, certain genetic types of common variable immunodeficiency are used to illustrate that inherited null mutations can take decades to manifest immunologically. Summary Both genetic mechanisms and environmental factors can account for adult-onset infectious and non-infectious complications as manifestations of disorders that typically present in childhood. This emphasizes the potential complexity in the relationship between genotype and phenotype with natural human mutations.

show abstract

“…The clinical presentation of patients with CVID is wide an made by exclusion of other possible causes [5], which can sometimes lead to a diagnosis reclassification after identification of genetic mutations or occurrence of new biological evidence or symptoms. Few CVID patients were reclassified to XLA (X-linked agammaglobulinemia) when a mutation in the BTK gene was found (OMIM: *300300) [6][7][8][9][10][11][12][13][14][15][16]. XLA is characterized by a failure during B-cell development [17,18], and is usually diagnosed before the age of 18 months, after the loss of maternal antibody protection [19], most of patients present an absence of B-cells and immunoglobulin.…”

Section: Introductionmentioning

confidence: 99%

Genetic screening of male patients with primary hypogammaglobulinemia can guide diagnosis and clinical management

et al. 2018

View full text Add to dashboard Cite

The precise diagnosis of an immunodeficiency is sometimes difficult to assess, especially due to the large spectrum of phenotypic variation reported among patients. Common variable immunodeficiency disorders (CVID) do not have, for a large part, an identified genetic cause. The identification of a causal genetic mutation is important to confirm, or in some cases correct, the diagnosis. We screened >150 male patients with hypogammaglobulinemia for mutations in three genes involved in pediatric X-linked primary immunoglobulin deficiency: CD40LG, SH2D1A and BTK. The SH2D1A screening allowed to reclassify two individuals with an initial CVID presentation as XLP after mutations identification. All these mutations were associated with a lack of protein expression. In addition, 4 patients with a primary diagnosis of CVID and one with a primary IgG subclass deficiency were requalified as XLA after identifying BTK mutations. Interestingly, two out of these 5 patients carried a damaging coding BTK mutation associated with a lower, but detectable, BTK expression in monocytes, suggesting that a dysfunctional protein explains the disease phenotype in these patients. In conclusion, our results advocate to include SH2D1A and BTK in newly developed targeted NGS genetic testing, to contribute to providing the most appropriate medical treatment and genetic counselling.

show abstract

X-linked agammaglobulinemia diagnosed late in life: case report and review of the literature

Cited by 36 publications

References 14 publications

Common Variable Immunodeficiency: Etiological and Treatment Issues

Common Variable Immunodeficiency: Etiological and Treatment Issues

Adult-onset presentations of genetic immunodeficiencies: genes can throw slow curves

Genetic screening of male patients with primary hypogammaglobulinemia can guide diagnosis and clinical management

Contact Info

Product

Resources

About