Alström syndrome: Renal findings in correlation with obesity, insulin resistance, dyslipidemia and cardiomyopathy in 38 patients prospectively evaluated at the NIH clinical center

Meryl Waldman, Joan Han, Daniela P. Reyes-Capo, Joy Bryant, Kathryn A. Carson, Baris Turkbey, Peter Choyke, Jürgen K. Naggert, William A. Gahl, Jan D. Marshall, Meral Gunay-Aygun

Research output: Contribution to journalArticle

Abstract

Alström Syndrome is a ciliopathy associated with obesity, insulin resistance/type 2 diabetes mellitus, cardiomyopathy, retinal degeneration, hearing loss, progressive liver and kidney disease, and normal cognitive function. ALMS1, the protein defective in this disorder, localizes to the cytoskeleton, microtubule organizing center, as well as the centrosomes and ciliary basal bodies and plays roles in formation and maintenance of cilia, cell cycle regulation, and endosomal trafficking. Kidney disease in this disorder has not been well characterized. We performed comprehensive multisystem evaluations on 38 patients. Kidney function decreased progressively; eGFR varied inversely with age (p = 0.002). Eighteen percent met the definition for chronic kidney disease (eGFR < 60 mL/min/1.73 m 2 and proteinuria); all were adults with median age of 32.8 (20.6–37.9) years. After adjusting for age, there were no significant associations of kidney dysfunction with type 2 diabetes mellitus, dyslipidemia, hypertension, cardiomyopathy or portal hypertension suggesting that kidney disease in AS is a primary manifestation of the syndrome due to lack of ALMS1 protein. Approximately one-third of patients had hyperechogenicity of the renal parenchyma on imaging. While strict control of type 2 diabetes mellitus may decrease kidney-related morbidity and mortality in Alström syndrome, identification of novel targeted therapies is needed.

Original languageEnglish (US)
Pages (from-to)181-191
Number of pages11
JournalMolecular Genetics and Metabolism
Volume125
Issue number1-2
DOIs
StatePublished - Sep 1 2018

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Dyslipidemias
Cardiomyopathies
Insulin Resistance
Kidney Diseases
Medical problems
Obesity
Insulin
Type 2 Diabetes Mellitus
Kidney
Microtubule-Organizing Center
Basal Bodies
Centrosome
Retinal Degeneration
Ciliary Body
Cilia
Audition
Portal Hypertension
Cytoskeleton
Chronic Renal Insufficiency
Proteinuria

All Science Journal Classification (ASJC) codes

  • Endocrinology, Diabetes and Metabolism
  • Biochemistry
  • Molecular Biology
  • Genetics
  • Endocrinology

Cite this

Alström syndrome : Renal findings in correlation with obesity, insulin resistance, dyslipidemia and cardiomyopathy in 38 patients prospectively evaluated at the NIH clinical center. / Waldman, Meryl; Han, Joan; Reyes-Capo, Daniela P.; Bryant, Joy; Carson, Kathryn A.; Turkbey, Baris; Choyke, Peter; Naggert, Jürgen K.; Gahl, William A.; Marshall, Jan D.; Gunay-Aygun, Meral.

In: Molecular Genetics and Metabolism, Vol. 125, No. 1-2, 01.09.2018, p. 181-191.

Research output: Contribution to journalArticle

Waldman, Meryl ; Han, Joan ; Reyes-Capo, Daniela P. ; Bryant, Joy ; Carson, Kathryn A. ; Turkbey, Baris ; Choyke, Peter ; Naggert, Jürgen K. ; Gahl, William A. ; Marshall, Jan D. ; Gunay-Aygun, Meral. / Alström syndrome : Renal findings in correlation with obesity, insulin resistance, dyslipidemia and cardiomyopathy in 38 patients prospectively evaluated at the NIH clinical center. In: Molecular Genetics and Metabolism. 2018 ; Vol. 125, No. 1-2. pp. 181-191.
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