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Key Features

  • Propionic acidemia is due to a defect in the biotin-containing enzyme propionyl-CoA carboxylase

  • Methylmalonic aciduria is due to a defect in methylmalonyl-CoA mutase, in either the mutase apoenzyme or in defects of its cofactor, adenosyl-B12 coenzyme

  • Some disorders of intracellular vitamin B12 metabolism affect only the synthesis of adenosyl-B12 (Cbl A, B, or D), whereas in others (Cbl C, D, F, J, X), the synthesis of methyl-B12 is also blocked, and hence homocysteine is also elevated in blood in addition to methylmalonic acid

  • All forms of propionic and methylmalonic acidemia are autosomal recessive traits (except for X-linked Cbl X) and can be diagnosed in utero

Clinical Findings

  • Clinical symptoms vary according to the location and severity of the enzyme block

  • Children with severe blocks have

    • Acute, life-threatening metabolic ketoacidosis

    • Hyperammonemia

    • Coma

    • Bone marrow depression in early infancy

    • Metabolic acidosis

    • Vomiting

    • Failure to thrive during the first few months of life

  • Most patients with severe disease have mild or moderate mental retardation

  • Late complications

    • Pancreatitis

    • Cardiomyopathy

    • Basal ganglia stroke

    • Interstitial nephritis (most common in methylmalonic aciduria)


  • Laboratory findings consist of increases in urinary organic acids derived from propionyl-CoA or methylmalonic acid

  • Hyperglycinemia can be present

  • In some forms of abnormal vitamin B12 metabolism, homocysteine can be elevated

  • Confirmation is by molecular analysis or by assays in fibroblasts


  • Patients with enzyme blocks in B12 metabolism usually respond to pharmacologic doses of vitamin B12 given subcutaneously or intramuscularly

  • Vitamin B12 nonresponsive methylmalonic acidemia and propionic acidemia require

    • Amino acid restriction

    • Strict prevention of catabolism

    • Carnitine supplementation to enhance propionylcarnitine excretion

  • Intermittent metronidazole can help reduce the propionate load from the gut

  • In the acute setting, hemodialysis or hemofiltration may be needed

  • Combined liver-renal transplantation is an option for patients with renal insufficiency

  • Liver transplantation has shown promise for patients with life-threatening cardiomyopathy

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