Abstract: PO1533
Late-Onset Hepatocyte Nuclear Factor 1β-Associated Kidney Disease
Session Information
- Cystic Kidney Diseases: Mechanisms, Genetics, and Treatment
October 22, 2020 | Location: On-Demand
Abstract Time: 10:00 AM - 12:00 PM
Category: Trainee Case Report
- 1001 Genetic Diseases of the Kidneys: Cystic
Authors
- Alahiri, Emad, Montefiore Medical Center, Bronx, New York, United States
- Fisher, Molly, Montefiore Medical Center, Bronx, New York, United States
Introduction
Hepatocyte Nuclear Factor 1β (HNF1β) is an important transcription factor for kidney development. HNF1β mutations are rare, associated with multisystemic disease and heterogeneous kidney involvement. HNF1β-associated kidney disease may not manifest until adulthood. We present a case of an older female with chronic hypomagnesemia and kidney cysts due to a heterozygous deletion in the HNF1β gene.
Case Description
66 y/o Puerto Rican female with a history of recurrent urinary tract infections, pre-diabetes, hypertension, arthritis, congenital absence of left ovary and baseline SCr 0.9 mg/dL was referred for evaluation of bilateral kidney cysts and chronic hypomagnesemia. Review of magnetic resonance imaging and ultrasound going back to 2003 showed normal sized kidneys and presence of more than 4 cysts in each kidney, some of which were mildly complex. No extrarenal cysts were noted and she denied family history of kidney cysts. Chronic symptomatic hypomagnesemia was present since at least 2015 with serum magnesium ranging from 1.1-1.6 meq/L, resulting in emergency room visits and hospitalizations. Fractional excretion of magnesium was 29%, consistent with renal magnesium wasting. Serum potassium and bicarbonate were normal. Intact parathyroid hormone ranged from 83-112 pg/mL but serum calcium, phosphorus, 25 dihydroxyvitamin D were normal. Urinalysis was bland. She was sent for genetic testing and underwent whole exome sequencing. Results demonstrated a heterozygous deletion in the HNF1β gene consistent with HNF1β nephropathy. She was started on amiloride and slow release magnesium supplementation with near normalization of her serum magnesium.
Discussion
HNF1β-associated kidney disease is a challenging diagnosis given extreme variability in phenotypes. De novo mutations occur in up to half of patients leading to diagnosis later in life. Our patient’s constellation of medical problems including glucose intolerance, mild hyperparathyroidism, hypomagnesemia, unilateral ovary agenesis and genitourinary (GU) tract abnormalities are all features of HNF1β-associated kidney disease. This diagnosis should not be overlooked in patients with GU abnormalities, electrolytes disturbances and/or signs of tubulointerstitial kidney disease. Additionally, these patients should be monitored for progressive kidney disease and undergo periodic screening for renal cell carcinoma.