Abstract: PUB127
Genetic-Phenotypic Discordance in Suspected Liddle-Like Syndrome
Session Information
Category: Genetic Diseases of the Kidneys
- 1202 Genetic Diseases of the Kidneys: Non-Cystic (Complex and Non-Cystic Monogenic)
Author
- Nawaz, Iqra, SUNY The State University of New York, Syracuse, New York, United States
Introduction
Liddle syndrome is a rare autosomal dominant cause of resistant hypertension that is frequently underrecognized and misdiagnosed as primary aldosteronism or essential hypertension. Clinical suspicion is raised in patients with resistant hypertension, hypokalemia, and metabolic alkalosis; however, genetic testing may not always confirm the diagnosis.
Case Description
A 48-year-old male with longstanding hypertension diagnosed at age 30 was referred to nephrology for resistant hypertension. Laboratory evaluation demonstrated intermittent hypokalemia (<3.0 mEq/L) with metabolic alkalosis (bicarbonate >30 mEq/L), suppressed renin activity, and low aldosterone levels. Extensive secondary hypertension workup, including renal artery Doppler ultrasound, 24-hour urine metanephrines, abdominal MRI, cortisol, and TSH, was unrevealing. Urinalysis showed no hematuria or proteinuria, while SPEP/UPEP were normal. Echocardiography demonstrated mild left ventricular hypertrophy. There was no history of licorice use; however, family history was notable for hypertension in his father and paternal grandfather. Given strong clinical suspicion for Liddle-like physiology, the patient was started on the ENaC inhibitor Amiloride, ultimately requiring 20 mg daily for optimal blood pressure control. Following initiation of therapy, potassium and bicarbonate levels normalized. Patient discontinued Amiloride, resulting in recurrent hypertensive urgencies with associated hypokalemia and metabolic alkalosis, which again improved after Amiloride reinitiation. Genetic testing, including a monogenic hypertension and renal tubular disorders panel, revealed no pathogenic variants.
Discussion
Genotype–phenotype discordance has been increasingly recognized in patients with suspected Liddle-like syndrome, with some patients demonstrating classic clinical features despite negative genetic testing. In such cases, strong clinical phenotype and therapeutic response to ENaC inhibition may remain critical for diagnosis and long-term management.
Biochemical evaluation
| Serum Creatinine Renin Activity Aldosterone Normetanephrine Metanephrine Morning Cortisol TSH Urine K Urine Cr FeK | 0.9 mg/dL <0.167 ng/mL/hr 10 ng/dL 279 µg /24 hr 95 µg /24 hr 15 µg /dL 1.7 mIU/L 30 mmol/L 30 mg/dL 31% |
Serum Potassium and Bicarbonate trends following ENaC therapy initiation
Invitae Diagnostic Testing Results