Abstract: SA-PO821
The Progressive Decline of Kidney Function: Can We Have an Answer?
Session Information
- Genetic Diseases: Glomerulopathies - II
November 04, 2023 | Location: Exhibit Hall, Pennsylvania Convention Center
Abstract Time: 10:00 AM - 12:00 PM
Category: Genetic Diseases of the Kidneys
- 1202 Genetic Diseases of the Kidneys: Non-Cystic
Authors
- Abraamyan, Feruza, Mercy Health St Elizabeth Youngstown Hospital, Youngstown, Ohio, United States
- Sarac, Erdal, Mercy Health St Elizabeth Youngstown Hospital, Youngstown, Ohio, United States
- Negrete, Hilmer O., Mercy Health St Elizabeth Youngstown Hospital, Youngstown, Ohio, United States
Introduction
With the field of nephrology moving towards personalized medicine, genetics is taking its lead in providing patient care. Tuberous sclerosis complex (TSC) is an inherited disorder with lesions involving multiple organs, including the kidneys. While TSC is often diagnosed during childhood, some cases might not be recognized until adulthood.
Case Description
Here we present a 58 y.o. female with a history of breast cancer, seizures, parathyroid adenoma, strictures of the esophagus, dental pitting, oral fibromas, and hyperpigmented macules in the mouth, who was referred due to abnormal results: Creatinine 1.6 mg/dL, eGFR 33 mL/min/1.73. Her family history was positive for cancer in her father of unknown origin. Her kidney ultrasound showed multiple fat-density tumors within both kidneys and a left renal cortical cyst. CT abdomen demonstrated bilaterally enlarged kidneys with innumerable fat-containing lesions consistent with angiomyolipomas. CT head revealed intracranial calcifications with MRI positive for cortical and subcortical glioneuronal tumors and giant cell gliocytoma. On CT lungs, there were numerous scattered thin-walled cysts throughout both lungs with numerous scattered nodules. Recently, the patient underwent surgery to remove a 4.4 cm invasive adenocarcinoma of the rectum with negative margins and lymph nodes for malignancy on biopsy. Genetic testing was performed that showed heterozygous pathogenic missense mutation in the TSC2 gene with AD inheritance mode: c.1832G>A (p. Arg611Gln), NM_000548.5 supporting the diagnosis of TSC. Multiple laboratories in the Clinvar Database predict this variant as pathogenic and absent in the gnomAD dataset, which tells about the rarity of this mutation. Silico's analysis supports the idea that this missense variant disrupts protein structure/function. Inactivation of the tuberin-hamartin complex leads to cell proliferation and size discoordination, which explains the pathophysiologic mechanism of our patient`s phenotype.
Discussion
Currently, the patient continues to have progressive worsening of kidney function with a creatinine of 3.5-3.7 mg/dL. However, knowing the exact diagnosis helped with the appropriate management, prognosis and offered potential screening and diagnosing opportunities for family members.