Abstract: PUB184
Unexplained Renal Cysts Uncover Hereditary Transthyretin Amyloidosis
Session Information
Category: Genetic Diseases of the Kidneys
- 1201 Genetic Diseases of the Kidneys: Monogenic Kidney Diseases
Authors
- Emlemdi, Mohamed, The Ohio State University College of Medicine, Columbus, Ohio, United States
- Yau, Amy, The Ohio State University Wexner Medical Center Division of Nephrology, Columbus, Ohio, United States
Introduction
Hereditary transthyretin (ATTRv) amyloidosis is a progressive multisystem disorder caused by misfolding and deposition of transthyretin protein, mostly in the heart and peripheral nerves. The Val142Ile (V122I) TTR variant, found in ~3.5% of the African American population, is well-known for cardiac involvement but less recognized for renal manifestations. We report a case where unexplained renal cysts led to genetic testing and diagnosis of ATTRv in a patient with otherwise unclassified renal disease.
Case Description
A 49-year-old African American man with hypertension and a 2-year history of primary hyperaldosteronism was followed by nephrology. Serum creatinine was 1.3 mg/dL, eGFR 66 mL/min/1.73m2 and urinalysis negative for protein and blood. An unexplained right carotid dissection prompted abdominal CT revealing multiple bilateral renal cysts up to 6.8 cm and small hepatic cysts up to 1.5 cm. There was no personal or family history of polycystic kidney disease and no known lithium or nephrotoxin exposure. Notably, his father had heart failure of unclear etiology. A next-generation sequencing panel was pursued and revealed a heterozygous pathogenic TTR variant (c.424G>A, p.Val142Ile), confirming ATTRv. Testing for ADPKD-related genes was negative.
Individuals with Val142Ile have a 30-45% lifetime risk of developing heart failure, usually due to cardiac amyloid infiltration. While rarely linked to neuropathy or renal cysts, this variant may explain his renal disease given negative testing for other cystic causes.
Discussion
This case highlights genetic testing’s diagnostic value in chronic kidney disease (CKD) of unclear origin. The patient met screening criteria for autosomal dominant polycystic kidney disease, but the ATTRv diagnosis was unexpected. The presence of renal cysts without known hereditary or toxic cause led to genetic testing and ATTRv diagnosis. Though Val142lle is most often linked to late-onset cardiomyopathy, emerging reports suggest that renal involvement may be an underrecognized part of its phenotype. Usually identified via cardiac or neurologic signs, ATTRv can first present with renal imaging abnormalities. This case shows how atypical renal findings can serve as an entry point for identifying systemic disease. Broader use of genetic panels earlier in the CKD workup may facilitate timely diagnosis and inform targeted management strategies.