Abstract: PUB188
Uncovering Dent Disease in Adulthood: A Case of Incidental Severe Medullary Nephrocalcinosis
Session Information
Category: Genetic Diseases of the Kidneys
- 1201 Genetic Diseases of the Kidneys: Monogenic Kidney Diseases
Authors
- De la Pena, Anna Valeria, Rutgers Health, Jersey City, New Jersey, United States
- Butt, Faizan, Rutgers Health, Jersey City, New Jersey, United States
- Subedi, Sachita, Rutgers Health, Jersey City, New Jersey, United States
- Madigan, John D., Jersey City Medical Center, Jersey City, New Jersey, United States
Introduction
Dent disease is a rare X-linked recessive proximal tubulopathy that primarily affects males and is often diagnosed in childhood. Clinical manifestations vary widely, ranging from isolated proteinuria to rickets or recurrent nephrolithiasis. It is classically defined by a triad of low molecular weight proteinuria, hypercalciuria, and nephrocalcinosis or nephrolithiasis. Two genetic subtypes exist: Dent disease 1, caused by CLCN5 mutations, accounts for 60% of cases, while Dent disease 2, involving OCRL mutations, comprises approximately 15%.
Case Description
A 40-year-old male with no significant history presented with fever, dyspnea, and pleuritic chest pain. He was hypoxic, febrile, and diagnosed with multifocal pneumonia. CT imaging incidentally revealed severe bilateral medullary nephrocalcinosis. Labs showed acute kidney injury with creatinine 3.92 mg/dL (baseline 1.26), and urinalysis revealed proteinuria, hematuria, and pyuria. Given the nephrocalcinosis and renal dysfunction, a workup was initiated. Autoimmune and glomerulonephritis panels were negative. Genetic testing via Renasight panel identified a pathogenic hemizygous CLCN5 mutation (c.1909C>T, p.Arg637*) consistent with Dent disease type 1. The patient was started on hydrochlorothiazide, advised on dietary modifications, and referred for genetic counseling. Renal function stabilized on follow-up with creatinine ~1.9 and eGFR 45–50.
Discussion
The uniqueness of this case stems in the rarity of the condition (approximately 250 affected families documented worldwide) and the atypical presentation. Although Dent disease is usually diagnosed in childhood, it can remain unrecognized until adulthood. Our patient exhibited proteinuria, nephrocalcinosis, and renal insufficiency—key features of Dent disease—but lacked documented hypercalciuria, likely masked by AKI. The phenotypic overlap with other renal conditions underscores the need for genetic testing to confirm diagnosis and guide management. Early identification allows for supportive measures that may slow disease progression.
Take-away points:
1.Inherited tubulopathies like Dent disease should be considered in adults with unexplained nephrocalcinosis
2.Genetic testing is crucial to confirm diagnosis and inform management.
3.Early diagnosis and supportive care can help slow progression to chronic kidney disease.