Congenital hyperinsulinism in two siblings with ABCC8 mutation: same genotype, different phenotypes

Area of Science:

• Genetics
• Pediatrics
• Endocrinology

Background:

• Congenital hyperinsulinism (CHI) is a rare genetic disorder characterized by dysregulated insulin secretion.
• Mutations in ABCC8 and KCNJ11 are the most frequent genetic causes of CHI.
• Current treatments include diazoxide, somatostatin analogues, and surgery for focal forms.

Observation:

• This report details two siblings diagnosed with diffuse CHI caused by a compound ABCC8 mutation (c.3576delG and c.742C>T).
• Both siblings presented with persistent hypoketotic hyperinsulinemic hypoglycemia in the neonatal period.
• Patient 1 underwent pancreatectomy and developed neurological deficits, including epilepsy, while Patient 2 had normal neurodevelopment.

Findings:

• Neither sibling responded to diazoxide therapy.
• Both siblings showed a positive response to somatostatin analogues.
• Despite sharing the same genotype, the siblings exhibited disparate clinical and neurological outcomes.

Implications:

• Timely and informed medical care, informed by prior sibling experience, can significantly impact patient outcomes in genetic disorders.
• This case highlights the potential for improved neurodevelopmental outcomes in congenital hyperinsulinism through vigilant monitoring and tailored therapeutic strategies.
• Understanding genotype-phenotype correlations and the impact of early intervention is crucial for managing complex genetic conditions like CHI.