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A newborn presents with poor feeding, lethargy, and failure to thrive. Labs show elevated methylmalonic acid AND homocysteine, with megaloblastic anemia. Ophthalmologic exam reveals progressive macular degeneration.
AR; MMACHC (metabolism of cobalamin associated C)
- Most common inborn error of cobalamin (vitamin B12) metabolism
- Impairs conversion of cobalamin to both adenosylcobalamin (needed by methylmalonyl-CoA mutase) and methylcobalamin (needed by methionine synthase)
- Results in combined methylmalonic acidemia AND homocystinuria (distinguishes from isolated MMA)
- Combined methylmalonic acidemia + homocystinuria (biochemical hallmark)
- Megaloblastic anemia (unlike isolated MMA)
- Progressive macular degeneration / retinopathy
- Developmental delay, seizures
- Thrombotic microangiopathy (hemolytic uremic syndrome)
- On RUSP (detected via elevated C3-carnitine)
- Newborn screening: elevated C3-carnitine (propionylcarnitine)
- Confirmatory: elevated urine methylmalonic acid + plasma homocysteine
- MMACHC gene testing
- Low methionine (vs elevated in classical homocystinuria)
- Hydroxocobalamin (IM injections): the preferred form of B12 supplementation
- Betaine (to lower homocysteine)
- Carnitine supplementation
- Protein restriction (mild)
- Ophthalmologic surveillance for macular changes
You can't "C" (see) with Cobalamin C: vision loss (macular degeneration) is a distinguishing feature of cblC compared to other organic acidemias.
"Combined" = Cobalamin C: cblC causes combined MMA + homocystinuria, unlike isolated MMA (MUT) or isolated homocystinuria (CBS). If you see both elevated on labs, think cblC.
MMACHC: MethylMalonic Acid + HomoCysteine are both elevated, hidden in the gene name.