Hyperinsulinemic Hypoglycemia Due to PMM2 Mutation in Two Siblings with Autosomal Recessive Polycystic Kidney Disease

Area of Science:

• Metabolic disorders
• Genetics
• Pediatrics

Background:

• Hyperinsulinemic hypoglycemia (HH) is a significant cause of persistent hypoglycemia in infants.
• PMM2 mutations are increasingly recognized as a cause of HH, often co-occurring with polycystic kidney disease (PKD).
• PMM2 deficiency, a common congenital disorder of glycosylation (CDG), can lead to various renal manifestations.

Observation:

• This report details two siblings with autosomal recessive polycystic kidney disease (ARPKD) presenting with severe infantile hypoglycemia.
• Both siblings exhibited biochemical markers consistent with HH, including elevated insulin and low beta-hydroxybutyrate.
• Genetic analysis confirmed PMM2 mutations in both affected siblings.

Findings:

• The study identifies a PMM2 mutation associated with both HH and ARPKD in non-consanguineous siblings.
• This genetic combination was previously reported in European descent patients, but this case expands the observed demographic.
• The findings suggest PMM2 mutations disrupt glycosylation, leading to cystic kidneys and altered insulin secretion.

Implications:

• This case broadens the understanding of PMM2-CDG and its phenotypic spectrum.
• It highlights the importance of genetic testing for PMM2 mutations in infants with unexplained hypoglycemia and cystic kidney disease.
• Further research into the molecular mechanisms linking PMM2 mutations to renal and metabolic dysfunction is warranted.