Cobalamin C Disease

Methylmalonic acuduria with homocystinuria

• Most common inborn error of vitamin B12 metabolism
• Early Onset (First year of life)
  • Neurologic & Cognitive Deterioration
  • Pancytopenia
  • Megaloblastic anemia
  • Progressive Retinopathy
• Later Childhood (>6 years) Onset
  • Gait abnormalities
  • Extrapyramidal symptoms
  • Psychiatric disturbances
  • Dementia
  • Cognitive Disability
  • No retinopathy

• Retinopathy
  • Spectrum from mild nerve fiber layer loss to advanced macular and optic nerve atrophy with “bone spicule” pigmentation
  • Reduced ERG responses
• Nystagmus

• Failure to thrive, poor feeding, vomiting
• Microcephaly, brain malformations
• Hypotonia
• Speech delay
• Seizures

• Mutation in MMACHC gene
  • Gene product converts dietary vitamin B12 to the metabolically active forms
• Treatment includes supplementation with:
  • hydroxycobalamin
  • betaine
  • folinic acid

• Ocular Phenotype in Patients with methylmalonic aciduria and homocystinuria, cobalamin C type. J AAPOS 2008
• Methylmalonic aciduria and homocystinuria-associated maculopathy. Eye 2010
• The Adolescent and adult form of cobalamin C disease: clinical and molecular spectrum. J Neurol Neurosurg Psychiatry 2008