Persistent Hypoglycemia, Newborn, N/IICU — Etiologies of Hyperinsulinism — Clinical Pathway: ICU

Newborn Persistent Hypoglycemia Clinical Pathway — N/IICU

Etiologies of Hyperinsulinism

Most Common Etiologies Listed Below

Condition Type Genes Features
Congenital Hyperinsulinism KATP-HI
  • ABCC8, KCNJ11
  • Diffuse
    • Autosomal recessive or autosomal dominant (less common)
  • Focal
    • Paternally inherited recessive mutation
  • Most common congenital form
  • High GIR, protein-induced hypoglycemia
  • Occurs in focal and diffuse forms
  • Majority unresponsive to diazoxide
  • Diffuse
    • Beta-cell hyperactivity throughout pancreas. Requires intensive medical therapy vs. 98% pancreatectomy
  • Focal
    • Localized area of beta cell overgrowth. Requires 18-FDOPA PET to localize lesion. Can be cured with surgical resection of lesion.
GDH-HI GLUD1
  • Hyperinsulinism-Hyperammonemia syndrome
  • Protein-induced hypoglycemia
  • Elevated ammonia levels
  • Seizures, learning disabilities
  • Diazoxide responsive
Glucokinase- HI GCK Variable severity and responsiveness to diazoxide
HNF4α-HI and HNF1α-HI HNF4A, HNF1A
  • Diazoxide responsive
  • Risk of diabetes later in life
Transient Hyperinsulinism Infant of diabetic mother Acquired Typically resolves within a few days of life
Perinatal stress Acquired
  • IUGR, birth asphyxia, prematurity, congenital heart disease
  • Most are diazoxide responsive
  • Hypoglycemia resolves within 3-6 months
Syndromic Hyperinsulinism Beckwith-Wiedemann syndrome Multiple mechanisms involving imprinted region of 11p15
  • Macroglossia
  • Omphalocele
  • Hemihypertrophy
  • Embryonal tumors
Kabuki syndrome KMT2D, KDM6A
  • Characteristic facial features
  • Cardiac defects
  • Fetal finger pads
  • Short stature
  • Developmental delay
Turner syndrome Monosomy X
  • Short stature
  • Premature ovarian failure
  • Cardiac and renal anomalies