Case Report: Exome Sequencing Reveals LRBA Deficiency in a Patient With End-Stage Renal Disease

Frontiers in Pediatrics

article

Christina Taylan¹  Andrea Wenzel²  Florian Erger²  Heike Göbel⁴  Lutz T. Weber¹  Bodo B. Beck² 

[1] Department of Pediatrics, Faculty of Medicine and University Hospital Cologne, University of Cologne;Faculty of Medicine and University Hospital Cologne, Institute of Human Genetics, University of Cologne;Center for Molecular Medicine, Faculty of Medicine and University Hospital Cologne, University of Cologne;Department of Pathology, Faculty of Medicine and University Hospital Cologne, University of Cologne

关键词: lipopolysaccharide-responsive beige-like anchor protein (LRBA);    renal failure;    kidney transplantation;    tubulointerstitial kidney disease;    whole-exome sequencing;   

DOI  :  10.3389/fped.2020.00042

学科分类：社会科学、人文和艺术（综合）

来源: Frontiers

【 摘 要 】

Background: Lipopolysaccharide-responsive and beige-like anchor protein (LRBA) deficiency is characterized by autoimmunity, chronic diarrhea, and immunodeficiency. Minor renal manifestations have been found in a few patients, but kidney disease has not been systematically studied and may remain underdiagnosed in this highly variable entity. Results: Our patient initially presented with pancytopenia, enteropathy, hypogammaglobulinemia, and failure to thrive at the age of 15 months. Chronic kidney disease was diagnosed at 6 years. A renal biopsy taken at 11 years of age showed interstitial nephritis. The patient progressed rapidly to end-stage renal disease (ESRD) and underwent kidney transplantation at the age of 12 years. Bronchiolitis obliterans, post-transplant lymphoproliferative disease (PTLD), and chronic rejection complicated the post-transplant management. Graft loss required reinstitution of hemodialysis within 3 years. After negative results of different targeted sequencing strategies, exome sequencing identified a homozygous nonsense mutation (p.Q1010 * ) in the LRBA gene more than 21 years after the patient's initial presentation. Conclusions: We report here the development of ESRD and long-term follow-up in a patient with LRBA deficiency. A molecular diagnosis in rare (kidney) disease like LRBA deficiency bears many advantages over a descriptive diagnosis. A precise diagnosis may result in improved (symptomatic) treatment and allows differentiating treatment- and procedure-related complications from manifestations of the primary disease.

【 授权许可】

CC BY