Wolfram syndrome

Definition

• Congenital syndrome characterized by diabetes mellitus and optic atrophy, along with other associated issues
• Also known as DIDMOAD
  • Diabetes insipidus (central)
  • Diabetes mellitus (non-autoimmune type 1)
  • Optic atrophy
  • Deafness
• There is also Type 2 Wolfram syndrome
  • GI ulcers with resulting bleeds
  • No DI

Pathophysiology

• WFS1 mutation (encodes Wolframin protein)
• Transmembrane protein present in many systems
  • Pancreas, brain, spinal cord, heart, muscle >> liver, kidneys
• Putative functions include membrane trafficking, secreation, processing, and regulation of ER calcium homeostasis

Epidemiology

• Prevalence 1/750,000; highest in Lebanese (1/68,000)
• DM
  • Insulin-dependent, T1DM-style from destruction of pancreatic cell
  • Presents in childhood
  • 1/150 cases of T1DM are Wolfram syndrome

Clinical Manifestations

• Diabetes mellitus presents in childhood
• Diabetes insipidus is central and presents in teenage years or early adulthood
• Hypogonadism M>F
• Hypothalamic pituitarism: GH deficiency, cotricotropin deficiency