StudyRareStudyRare

Methylmalonic acidemia (MMA)

Log in to star

Last updated 2mo ago

Log in to add personal notes on this page.

A newborn becomes lethargic with metabolic acidosis, hyperammonemia, and ketosis. Urine organic acids show markedly elevated methylmalonic acid.

AR

  • MUT (methylmalonyl-CoA mutase): mut0 or mut-
  • MMAA, MMAB (B12 metabolism): some B12-responsive
  • Metabolic acidosis with high anion gap
  • Hyperammonemia, hypoglycemia, ketosis
  • Neutropenia, thrombocytopenia
  • Long-term: renal failure, basal ganglia injury
  • On RUSP
  • Detected on newborn screening: elevated C3 (propionylcarnitine), often with elevated C3/C2 ratio
  • Urine organic acids: markedly elevated methylmalonic acid (with methylcitrate); plasma homocysteine distinguishes combined cobalamin defects
  • Confirmation: molecular testing (MUT, MMAA, MMAB); cobalamin-responsiveness assessed by B12 trial
  • Protein restriction, B12 (cobalamin) trial, carnitine, liver/kidney transplant

"Micturition in Methylmalonic": MMA patients develop renal failure (kidney = "micturition" = peeing). Contrast with propionic acidemia, where patients develop issues with the Pump (cardiac disease).

NBS: High C3 (propionylcarnitine): elevated C3 on newborn screening acylcarnitine profile (same marker as propionic acidemia).

VoMIT amino acids: Valine, Methionine, Isoleucine, Threonine are the precursors that feed into the propionyl-CoA/methylmalonyl-CoA pathway. Restrict these in the diet.

Reference Links