GSD Type 4

Also known as Andersen Disease, Brancher Deficiency

Defect Defective glycogen-branching enzyme activity.

  • Congenital neuromuscular form
  • Childhood neuromuscular form - both are associated with isolated or predominant muscle involvement ,with the development of myopathy (muscle weakness) or cardiomyopathy at birth or during childhood.
  • Perinatal form severe neuromuscular involvement and death.
  • Adult Polyglucosan body disease (APBD) – a subset of which have deficient glycogen-

Branching enzyme activity and diffuse CNS and peripheral nervous system dysfunction.

Cause Defect in the gene that encodes for the glycogen-branching enzyme (GBE1) located on the chromosome band 3p12.This specific enzyme increases the number of branch points during glycogen synthesis.

Incidence An uncommon form of GSD accounting approximately 3% of all cases.

Signs & Symptoms

  • Classic presentation involves development of hepatospenomegaly and failure to thrive in the first year of life.
  • A milder congenital form is associated with hypotonia (weak muscles) and gross motor delay, without affecting the liver and the heart.
  • Patients with progressive liver cirrhosis and associated portal hypertension may also present itching, fatigue, Anorexia (loss of appetite), weakness, jaundice (yellowish discoloration of the skin & mucous membranes), nose bleed, and easy bruising.
  • May present cardiomyopathy
  • Patients with APBD will present muscle weakness, fatigue, gait disturbance, voiding difficulties, peripheral neuropathy and mild cognitive impairment and dementia.

Diagnosis

  • Laboratory studies
  • Imaging studies ( Ultrasound, CT Scan, MRI, Echocardiography, Proton MR spectroscopy)
  • Liver biopsy or biopsy of affected organs

Treatment

  • Medical Consults – based on organ affectation.
  • Medications – depending on organ involvement
  • Dietary – to provide adequate nutrient intake to maintain normal blood sugar levels and improve liver functions.
  • Surgical – liver transplant.

Prognosis

  • Poor with perinatal-onset (period between birth to five months) form who does not undergo liver transplantation.
  • Long-term for those classic GSD type IV who has undergome transplantation depending on the extent, severity and progression of this multisystem condition.