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Kidney Week

Abstract: SA-PO523

A Novel Pathogenic Mutation in Alström Syndrome Causing CKD

Session Information

  • Genetic Diseases: Diagnosis
    November 05, 2022 | Location: Exhibit Hall, Orange County Convention Center‚ West Building
    Abstract Time: 10:00 AM - 12:00 PM

Category: Genetic Diseases of the Kidneys

  • 1102 Genetic Diseases of the Kidneys: Non-Cystic

Authors

  • Yahr, Jordana, Cleveland Clinic, Cleveland, Ohio, United States
  • Hassanein, Mohamed, University of Mississippi Medical Center, Jackson, Mississippi, United States
  • Rincon-Choles, Hernan, Cleveland Clinic, Cleveland, Ohio, United States
Introduction

Alström Syndrome is a rare progressive multi-system disorder caused by mutations in the ALMS1 gene. It is inherited in an autosomal recessive fashion. It is estimated to occur in 1 of every 1,000,000 live births. The disease is characterized by visual defects (rod-cone dystrophy), sensorineural hearing loss, insulin resistance, cardiomyopathy, nonalcoholic fatty liver disease, and chronic kidney disease (CKD). We present a case of progressive kidney dysfunction in a patient with Alström syndrome due to a novel mutation in the ALMS1 gene.

Case Description

A 21-year-old female patient was referred to the nephrology clinic for evaluation of CKD. Her medical history included obesity, developmental delay in childhood, precocious puberty at age 7, hearing loss, and vision impairment. Genetic testing for Alström syndrome was performed and showed a compound heterozygous finding of c.5166dupA and c.7126dupA in the ALMS1 gene, both novel pathogenic mutations, resulting in a frameshift mutation with premature protein termination. She eventually developed CKD, hepatic steatosis, and type II diabetes mellitus, all consistent with Alström syndrome. Her brother demonstrated a similar clinical syndrome. Her CKD workup included normal complement levels, negative antinuclear antibody, negative viral hepatitis testing, urinalysis with intermittent microscopic hematuria, protein to creatinine ratio 0.4 g/g, albumin/creatinine ratio 204 mg/g, and structurally normal kidneys on ultrasound. Over the next 8 years, her CKD progressed to stage IIIb with a baseline creatinine of 2.0-2.4 mg/dL. She was treated with aggressive glucose and blood pressure control including an angiotensin receptor blocker and a sodium-glucose cotransporter-2 (SGLT2) inhibitor.

Discussion

Alström syndrome is a rare cause of CKD but should be considered in those presenting with consistent features. Kidney impairment is characterized by decreased glomerular filtration rate, microalbuminuria without overt proteinuria, interstitial fibrosis, glomerular hyalinosis, and tubular atrophy. Genetic testing has become the hallmark of diagnosis. We report a novel mutation in the ALMS1 gene resulting in Alström syndrome. While no specific treatment exists, treatment should be targeted at organ specific complications of the disease.