Case Report: Exome Sequencing Reveals LRBA Deficiency in a Patient With End-Stage Renal Disease
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 unde...
| Main Authors: | , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
Frontiers Media S.A.
2020-03-01
|
| Series: | Frontiers in Pediatrics |
| Subjects: | |
| Online Access: | https://www.frontiersin.org/article/10.3389/fped.2020.00042/full |
| _version_ | 1819159972270833664 |
|---|---|
| author | Christina Taylan Andrea Wenzel Andrea Wenzel Florian Erger Florian Erger Heike Göbel Lutz T. Weber Bodo B. Beck Bodo B. Beck |
| author_facet | Christina Taylan Andrea Wenzel Andrea Wenzel Florian Erger Florian Erger Heike Göbel Lutz T. Weber Bodo B. Beck Bodo B. Beck |
| author_sort | Christina Taylan |
| collection | DOAJ |
| description | 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. |
| first_indexed | 2024-12-22T16:49:02Z |
| format | Article |
| id | doaj.art-a667828b45b0463f8b9068035b687f51 |
| institution | Directory Open Access Journal |
| issn | 2296-2360 |
| language | English |
| last_indexed | 2024-12-22T16:49:02Z |
| publishDate | 2020-03-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Pediatrics |
| spelling | doaj.art-a667828b45b0463f8b9068035b687f512022-12-21T18:19:38ZengFrontiers Media S.A.Frontiers in Pediatrics2296-23602020-03-01810.3389/fped.2020.00042507427Case Report: Exome Sequencing Reveals LRBA Deficiency in a Patient With End-Stage Renal DiseaseChristina Taylan0Andrea Wenzel1Andrea Wenzel2Florian Erger3Florian Erger4Heike Göbel5Lutz T. Weber6Bodo B. Beck7Bodo B. Beck8Department of Pediatrics, Faculty of Medicine and University Hospital Cologne, University of Cologne, Cologne, GermanyFaculty of Medicine and University Hospital Cologne, Institute of Human Genetics, University of Cologne, Cologne, GermanyCenter for Molecular Medicine, Faculty of Medicine and University Hospital Cologne, University of Cologne, Cologne, GermanyFaculty of Medicine and University Hospital Cologne, Institute of Human Genetics, University of Cologne, Cologne, GermanyCenter for Molecular Medicine, Faculty of Medicine and University Hospital Cologne, University of Cologne, Cologne, GermanyDepartment of Pathology, Faculty of Medicine and University Hospital Cologne, University of Cologne, Cologne, GermanyDepartment of Pediatrics, Faculty of Medicine and University Hospital Cologne, University of Cologne, Cologne, GermanyFaculty of Medicine and University Hospital Cologne, Institute of Human Genetics, University of Cologne, Cologne, GermanyCenter for Molecular Medicine, Faculty of Medicine and University Hospital Cologne, University of Cologne, Cologne, GermanyBackground: 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.https://www.frontiersin.org/article/10.3389/fped.2020.00042/fulllipopolysaccharide-responsive beige-like anchor protein (LRBA)renal failurekidney transplantationtubulointerstitial kidney diseasewhole-exome sequencing |
| spellingShingle | Christina Taylan Andrea Wenzel Andrea Wenzel Florian Erger Florian Erger Heike Göbel Lutz T. Weber Bodo B. Beck Bodo B. Beck Case Report: Exome Sequencing Reveals LRBA Deficiency in a Patient With End-Stage Renal Disease Frontiers in Pediatrics lipopolysaccharide-responsive beige-like anchor protein (LRBA) renal failure kidney transplantation tubulointerstitial kidney disease whole-exome sequencing |
| title | Case Report: Exome Sequencing Reveals LRBA Deficiency in a Patient With End-Stage Renal Disease |
| title_full | Case Report: Exome Sequencing Reveals LRBA Deficiency in a Patient With End-Stage Renal Disease |
| title_fullStr | Case Report: Exome Sequencing Reveals LRBA Deficiency in a Patient With End-Stage Renal Disease |
| title_full_unstemmed | Case Report: Exome Sequencing Reveals LRBA Deficiency in a Patient With End-Stage Renal Disease |
| title_short | Case Report: Exome Sequencing Reveals LRBA Deficiency in a Patient With End-Stage Renal Disease |
| title_sort | case report exome sequencing reveals lrba deficiency in a patient with end stage renal disease |
| topic | lipopolysaccharide-responsive beige-like anchor protein (LRBA) renal failure kidney transplantation tubulointerstitial kidney disease whole-exome sequencing |
| url | https://www.frontiersin.org/article/10.3389/fped.2020.00042/full |
| work_keys_str_mv | AT christinataylan casereportexomesequencingrevealslrbadeficiencyinapatientwithendstagerenaldisease AT andreawenzel casereportexomesequencingrevealslrbadeficiencyinapatientwithendstagerenaldisease AT andreawenzel casereportexomesequencingrevealslrbadeficiencyinapatientwithendstagerenaldisease AT florianerger casereportexomesequencingrevealslrbadeficiencyinapatientwithendstagerenaldisease AT florianerger casereportexomesequencingrevealslrbadeficiencyinapatientwithendstagerenaldisease AT heikegobel casereportexomesequencingrevealslrbadeficiencyinapatientwithendstagerenaldisease AT lutztweber casereportexomesequencingrevealslrbadeficiencyinapatientwithendstagerenaldisease AT bodobbeck casereportexomesequencingrevealslrbadeficiencyinapatientwithendstagerenaldisease AT bodobbeck casereportexomesequencingrevealslrbadeficiencyinapatientwithendstagerenaldisease |