Abstract Background Alström syndrome (AS), a monogenic form of obesity, is caused by recessive mutations in the centrosome- and basal body-associated gene, ALMS1. AS is characterized by retinal dystrophy, sensory hearing loss, cardiomyopathy, childhood obesity, and metabolic derangements. Objective We sought to characterize the endocrine and metabolic features of AS while accounting for obesity as a confounder by comparing patients with AS to BMI-matched controls. Methods We evaluated 38 patients with AS (age 2-38y) who were matched with 76 controls (age 2-48y) by age, sex, race, and BMI. Fasting biochemistries, mixed meal test (MMT), indirect calorimetry, DEXA, and MRI/MRS were performed. Results Frequent abnormalities in AS included 76% obesity, 37% type 2 diabetes (T2DM), 29% hypothyroidism (1/3-central, 2/3-primary), 3% central adrenal insufficiency, 57% adult hypogonadism (1/3-central, 2/3-primary), and 25% female hyperandrogenism. AS and controls had similar BMI-Z, body fat, waist circumference, abdominal visceral fat, muscle fat, resting energy expenditure (adjusted for lean mass), free fatty acids, glucagon, prolactin, ACTH, and cortisol. Compared to controls, AS were shorter and had lower IGF1 concentrations (p’s≤0.001). AS had significantly greater fasting and MMT insulin resistance indices, higher MMT glucose, insulin, and C-peptide values, higher hemoglobin A1c, and higher prevalence of T2DM (p’s<0.001). AS had significantly higher triglycerides, lower HDL-cholesterol, and a 10-fold greater prevalence of metabolic syndrome (p’s<0.001). AS demonstrated significantly greater liver triglyceride accumulation and higher transaminases (p’s<0.001). Conclusion Severe insulin resistance and T2DM are the hallmarks of AS. However, patients with AS may present with multiple other endocrinopathies affecting growth and development. Copyright © 2018 Endocrine Society
Journal of Clinical Endocrinology and Metabolism – Oxford University Press
Published: Apr 27, 2018
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