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Abstract: PO1867

Unusual Aggregation of Different Glomerulopathies in a Family Resolved by Genetic Testing

Session Information

Category: Trainee Case Report

  • 1203 Glomerular Diseases: Clinical, Outcomes, and Trials

Authors

  • Keskinyan, Vahakn S., Duke University, Durham, North Carolina, United States
  • Kumar, Reeti, Duke University, Durham, North Carolina, United States
  • Gbadegesin, Rasheed A., Duke University, Durham, North Carolina, United States
Introduction

Glomerulonephritis (GN) is a major cause of chronic kidney disease (CKD) in children. The conventional approach to diagnosis of GN includes clinical evaluation and in most cases kidney biopsy to make a definitive diagnosis. However, in many cases, clinical presentations of different GNs can overlap leading to uncertainty in diagnosis and management even after renal biopsy. In this report we identify a family with clinical diagnoses of post infectious glomerulonephritis (PIGN) and IgA nephropathy in a parent and two children. Renal biopsies were inconclusive and we were only able to make final diagnoses in each of the family members after genetic testing and reverse phenotyping.

Case Description

A previously healthy 7 year old male presented to the emergency department with hematuria, fever, and sore throat. Apart from being obese, his physical examination was unremarkable. Laboratory data was remarkable for microscopic hematuria and non-nephrotic range proteinuria. C3/C4 complements, ASO, anti-DNase b, anti-dsDNA, ANCA, and anti-GBM titers were all normal. A presumptive diagnosis of PIGN was made. However, he had persistent hematuria and proteinuria over the next 10 months. Further history at follow up revealed a history of IgA nephropathy in his mother and CKD of unclear etiology in his maternal grandfather. Renal biopsy was initially reported to be consistent with IgA nephropathy. However, because of the family history we carried out genetic testing and identified a rare hemizygous variant [c.3437G>A (p.Gly1146Glu)] in the gene COL4A5. COL4A staining was performed on the prior biopsy and staining pattern was consistent with COL4A5 disease. We confirmed that his mother also carried the same variant and she also has a history of hearing loss. Incidentally, his older brother presented a few weeks later with AKI and classical features of PIGN. His renal biopsy was consistent with PIGN and genetic testing in him was negative for the COL4A5 variant found in his brother and mother.

Discussion

This case highlights the utility of genetic testing and reverse phenotyping in resolving clinical diagnosis in families with unusual constellations of different glomerulopathies. We propose that clustering of different glomerular disease phenotypes in a family should be an indication for genetic testing.