Syndromic forms of congenital hyperinsulinism

Area of Science:

• Endocrinology and Genetics
• Pediatric Metabolism
• Rare Diseases

Background:

• Congenital hyperinsulinism (CHI), also known as hyperinsulinemic hypoglycemia (HH), is a primary cause of persistent hypoglycemia in infants and children.
• While often monogenic, CHI is also linked to various syndromic disorders, including overgrowth syndromes, developmental syndromes, and congenital disorders of glycosylation.

Purpose of the Study:

• To review syndromic conditions associated with CHI.
• To assess the evidence, prevalence, pathophysiology, and natural course of CHI within these syndromes.

Main Methods:

• Literature review of syndromic conditions associated with CHI.
• Assessment of evidence for CHI association, prevalence, pathophysiology, and clinical course.

Main Results:

• CHI is associated with diverse syndromes like Beckwith-Wiedemann, Sotos, Turner, Kabuki, Costello, and Timothy syndromes.
• Mechanisms of dysregulated glucose sensing and insulin secretion in syndromic CHI are often unclear and not linked to known CHI genes.
• The association between syndromes and CHI can be inconsistent, with metabolic disturbances frequently being transient.

Conclusions:

• CHI in syndromic conditions presents diagnostic challenges, especially in newborns with congenital anomalies.
• Early identification of neonatal hypoglycemia is crucial for timely diagnosis and intervention.
• A broad genetic workup may be necessary for infants with HH and associated medical issues.