"Please see this man with a 69-year history of hypoglycaemia"

Area of Science:

• Endocrinology
• Genetics
• Metabolic Disorders

Background:

• Mutations in the Hepatocyte Nuclear Factor 4 Alpha (HNF4A) gene are typically linked to hyperinsulinaemic hypoglycemia in infants.
• These mutations often lead to maturity-onset diabetes of the young (MODY) later in life.
• Genetic causes of hyperinsulinaemic hypoglycemia can exhibit variable clinical presentations.

Observation:

• A 69-year-old male with a family history of adult-onset diabetes presented with lifelong hypoglycemia.
• He was found to have a pathogenic HNF4A mutation.
• Continuous glucose monitoring revealed frequent early morning hypoglycemia, and low HbA1c levels were noted.

Findings:

• The patient's lifelong hypoglycemia was attributed to a pathogenic HNF4A mutation, a novel phenotype for this genetic alteration.
• The same HNF4A mutation presented with distinct clinical manifestations within the same family.
• Successful treatment was achieved using diazoxide, an established therapy for hyperinsulinaemic hypoglycemia.

Implications:

• Genetic causes of hyperinsulinaemic hypoglycemia can present with late-onset symptoms, challenging typical diagnostic patterns.
• Identifying these late-onset cases is crucial for establishing appropriate and effective treatment strategies.
• This case broadens the understanding of HNF4A mutation phenotypes and their variable expressivity.