LPS-responsive beige-like anchor protein deficiency is a rare genetic condition caused by the absence of LPS-responsive beige-like anchor protein (''

LRBA Lipopolysaccharide-responsive and beige-like anchor protein is a protein that in humans is encoded by the ''LRBA'' gene In biology, the word gene (from , ; "...Wilhelm Johannsen coined the word gene to describe the Mendelian units of hered ...

'').

Signs and symptoms

The presentation of this condition is variable making the diagnosis difficult. The most common features includeGámez-Díaz L, August D, Stepensky P, Revel-Vilk S, Seidel MG, Noriko M, Morio T, Worth AJJ, Blessing J, Van de Veerdonk F, Feuchtinger T, Kanariou M, Schmitt-Graeff A, Jung S, Seneviratne S, Burns S, Belohradsky BH, Rezaei N, Bakhtiar S, Speckmann C, Jordan M, Grimbacher B (2016) The extended phenotype of LPS-responsive beige-like anchor protein (LRBA) deficiency. J Allergy Clin Immunol 137(1):223-230 * Immune dysregulation (95%) * Organomegaly (86%) * Recurrent infections (71%) * Hypogammaglobulinemia (57%) * Granulomatous lymphocytic interstitial lung disease (38%) There is also a tendency to develop

inflammatory bowel disease Inflammatory bowel disease (IBD) is a group of inflammation, inflammatory conditions of the colon (anatomy), colon and small intestine, Crohn's disease and ulcerative colitis being the principal types. Crohn's disease affects the small intestine a ...

Genetics

The LBRA gene is located on the long arm of chromosome 4 (4q31.3).

Pathogenesis

LBRA protein interacts with the protein

CTLA4 CTLA-4 or CTLA4 (cytotoxic T-lymphocyte-associated protein 4), also known as CD152 (cluster of differentiation 152), is a protein receptor that functions as an immune checkpoint and downregulates immune responses. CTLA-4 is constitutively expres ...

. The absence of LBRA increases the turnover of CTLA4 and interferes with vesicle trafficking.

Diagnosis

Differential diagnosis

Common variable immunodeficiency Common variable immunodeficiency (CVID) is an immune disorder characterized by recurrent infections and low antibody levels, specifically in immunoglobulin (Ig) types IgG, IgM and IgA. Symptoms generally include high susceptibility to foreign i ...

IPEX syndrome Immunodysregulation polyendocrinopathy enteropathy X-linked (or IPEX) syndrome is a rare disease linked to the dysfunction of the gene encoding transcription factor forkhead box P3 (FOXP3), widely considered to be the master regulator of the regula ...

Management

Along with treatment for infections and other complications several additional treatments have been tried. These include hematopoietic stem cell transplantation, immunoglobulin replacement and immunosuppressive treatment.

History

This condition was first described in 2012.Lopez-Herrera G, Tampella G, Pan-Hammarstrom Q, Herholz P, Trujillo-Vargas CM, Phadwal K, Simon AK, Moutschen M, Etzioni A, Mory A, Srugo I, Melamed, D and 21 others. Deleterious mutations in LRBA are associated with a syndrome of immune deficiency and autoimmunity. Am J Hum Genet 90: 986-1001

References

External links

{{DEFAULTSORT:LPS-responsive beige-like anchor protein deficiency Syndromes Autosomal recessive disorders Genetic diseases and disorders Rare diseases