Genetic Obesity Syndrome: Alström syndrome

Alström syndrome is a rare autosomal recessive genetic disorder.

Key characteristics of Alstrom Syndrome:

• Cone-rod dystrophy
• Hearing loss
• Childhood truncal obesity
• Insulin resistance and hyperinsulinemia
• Type 2 diabetes
• Hypertriglyceridemia
• Short stature in adulthood
• Cardiomyopathy
• Progressive pulmonary, hepatic, and renal dysfunction
• Symptoms appear in infancy and worsen over time, leading to reduced life expectancy.

There is variability in age of onset and severity of symptoms, even within families, likely due to genetic background.

Etiology:

• Caused by mutations in the ALMS1 gene.
• ALMS1 consists of 23 exons and codes for a protein of 4,169 amino acids.
• Defects include insertions, deletions, and nonsense mutations leading to protein truncations, mainly in exons 8, 10, and 16.
• ALMS1 protein is present in centrosomes, basal bodies, and cytosol of affected tissues.
• Multiple alternate splice forms of the gene exist.
• The protein’s role as a ciliary protein explains the diverse symptoms and similarity to other ciliopathies like Bardet-Biedl syndrome.