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Kidney Week

Abstract: TH-PO801

Identifying Thrombotic Microangiopathy Mimics

Session Information

Category: Genetic Diseases of the Kidneys

  • 1002 Genetic Diseases of the Kidneys: Non-Cystic

Authors

  • Ghiringhelli Borsa, Nicolò, Molecular Otolaryngology and Renal Research Laboratories, The University of Iowa, Iowa City, Iowa, United States
  • Taylor, Amanda O., Molecular Otolaryngology and Renal Research Laboratories, The University of Iowa, Iowa City, Iowa, United States
  • Jones, Michael, Molecular Otolaryngology and Renal Research Laboratories, The University of Iowa, Iowa City, Iowa, United States
  • Meyer, Nicole, Molecular Otolaryngology and Renal Research Laboratories, The University of Iowa, Iowa City, Iowa, United States
  • Zhang, Yuzhou, Molecular Otolaryngology and Renal Research Laboratories, The University of Iowa, Iowa City, Iowa, United States
  • Nester, Carla Marie, Molecular Otolaryngology and Renal Research Laboratories, The University of Iowa, Iowa City, Iowa, United States
  • Smith, Richard J., Molecular Otolaryngology and Renal Research Laboratories, The University of Iowa, Iowa City, Iowa, United States
Background

Thrombocytopenia is one of the key diagnostic criteria for the clinical diagnosis of thrombotic microangiopathy (TMA). When thrombocytopenia presents with other hemolytic processes, distinguishing the correct diagnosis can be difficult. In an era of terminal complement blockade, the correct diagnosis is critical to determining the optimal treatment approach. Here we describe a cohort of patients clinically diagnosed with TMA but then incidentally identified to have a pathogenic variant in the glucose-6-phosphate dehydrogenase (G6PD) gene.

Methods

Targeted genomic enrichment with massive parallel sequencing (TGE+MPS) of genes implicated in TMA was used to screen 329 patients. Multiplex ligation-dependent probe amplification (MLPA) for copy-number variations (CNVs) in the CFH-CFHR5 region was also performed.

Results

Of 329 patients screened, 7 patients were positive for well-described, pathogenic G6PD variants including 3 with the Union variant, 3 with the Sassari variant and 1 with the Chatham variant. All variants identified have been described as class II variants (1-10% G6PD residual activity). Of the 7 patients, 5 carry at least one complement gene variant, including 3 variants of unknown significance (1 CFH and 2 CFI), 1 pathogenic variant (DGKE), and 1 likely pathogenic variant (CFHR5). MLPA detected a heterozygous deletion of CFHR1-CFHR4 in one patient while the remaining were unremarkable. Our findings indicate that approximately 2% of TMA diagnoses may be accounted for by G6PD deficiency.

Conclusion

G6PD deficiency should be included on the differential for someone diagnosed with a hemolytic anemia associated with thrombocytopenia. It remains unclear if G6PD deficiency plays a primary or a modifier role in the TMA-like presentation. Similarly, if G6PD deficiency is the primary etiologic agent, what role does enzyme deficiency play in the individual features of the underlying pathology of the TMA-like presentation (including thrombocytopenia and renal insufficiency) is unknown. Despite this gap in our understanding, considering G6PD deficiency on the differential has clear diagnostic and treatment implications. We conclude that G6PD gene testing is recommended in the workup of a clinical TMA, and G6PD enzyme testing is warranted when the acute process has resolved.

Funding

  • NIDDK Support