Insulin resistance syndrome in subjects with mutated RING finger protein TRIM37

Area of Science:

• Endocrinology
• Genetics
• Metabolic Disorders

Background:

• Mulibrey nanism (MUL) is a rare monogenic disorder characterized by prenatal growth failure and distinctive clinical features.
• MUL results from mutations in the TRIM37 gene, which encodes a peroxisomal protein with E3 ubiquitin-ligase activity.

Purpose of the Study:

• To investigate the impact of Mulibrey nanism on glucose and lipid metabolism across different age groups.
• To explore the relationship between TRIM37 gene mutations and the development of metabolic disturbances.

Main Methods:

• Clinical evaluation of 65 MUL patients (aged 1.1-55 years).
• Abdominal ultrasonography and laboratory measurements, including a 3-hour oral glucose tolerance test.
• Assessment of metabolic parameters such as fasting glucose, insulin, insulin sensitivity, and National Cholesterol Education Program criteria for metabolic syndrome.

Main Results:

• Significant age-dependent alterations in glucose and lipid metabolism observed in MUL patients.
• Children exhibited low fasting glucose and insulin, while adults showed high fasting and postload insulin levels (up to 1,450 mU/l).
• Marked decrease in glucose-to-insulin ratio and whole-body insulin sensitivity index with age; high prevalence of insulin resistance, fatty liver, type 2 diabetes, and metabolic syndrome in adults.

Conclusions:

• TRIM37 gene mutations in MUL are strongly associated with severe metabolic dysregulation, including insulin resistance and metabolic syndrome.
• The peroxisomal targeting and ubiquitin-ligase activity of TRIM37 may offer insights into metabolic syndrome development.
• Early and continuous metabolic monitoring is crucial for patients with Mulibrey nanism due to the high risk of developing diabetes and metabolic syndrome.