TY - JOUR
T1 - Therapeutic approaches to cobalamin-C methylmalonic acidemia and homocystinuria
AU - Bartholomew, Dennis W.
AU - Batshaw, Mark L.
AU - Allen, Robert H.
AU - Roe, Charles R.
AU - Rosenblatt, David
AU - Valle, David L.
AU - Francomano, Clair A.
N1 - Funding Information:
The cobalamin C B~ activation defect resulting in methyl-malon!c acidemia and homocystinuria (McKusick 27740) ~ is characterized by neurodevelopmental delay, failure to thrive, megaloblastic anemia, and pigmentary retinopathy. 2 The cellular uptake and processing of cobalamin are impaired, and the subsequent production of the active cofactors for homocysteine and methylmalonyl-CoA catabolism (methylcobalamin and adenosylcobalamin) is significantly reduced. Although intramuscular hydroxoco- Supported by Grant MO1-00052 from the National Institutes of Health. Submitted for publication June 15, 1987; accepted Aug. 10, 1987. Reprint requests: Mark L. Batshaw, MD, John F. Kennedy Institute, 707 N. Broadway, Baltimore, MD 21205.
PY - 1988/1
Y1 - 1988/1
N2 - The use of hydroxocobalamin (OH-B12), betaine, carnitine, and folinic acid were studied in two children with the cobalamin C form of methylmalonic acidemia and homocystinuria. When daily injections of 1 mg OH-B12 were discontinued for 3 weeks, there was no significant change in total plasma homocysteine or methionine levels and only a modest increase in methylmalonate. Orally administered OH-B12 1 mg/d in one patient was associated with an increase in plasma homocystine and a decrease in methionine within 1 month. Withdrawal of betaine 250 mg/kg/d was also associated with a rise in plasma homocystine and a fall in methionine levels. Carnitine 100 mg/kg/d led to an increase in urinary excretion of propionylcarnitine, but did not affect plasma methylmalonate levels. No beneficial biochemical effect of follinic acid could be documented at a dose of 25 mg/d. Our results suggest that daily injections of OH-B12 are not necessary to maintain metabolic control and that orally administered OH-B12 is unlikely to be effective. Betaine appears to act synergistically with OH-B12 and should be part of the treatment regimen. Although there are theoretical reasons for using l-carnitine and folinic acid, we could not document their effectiveness in these two patients.
AB - The use of hydroxocobalamin (OH-B12), betaine, carnitine, and folinic acid were studied in two children with the cobalamin C form of methylmalonic acidemia and homocystinuria. When daily injections of 1 mg OH-B12 were discontinued for 3 weeks, there was no significant change in total plasma homocysteine or methionine levels and only a modest increase in methylmalonate. Orally administered OH-B12 1 mg/d in one patient was associated with an increase in plasma homocystine and a decrease in methionine within 1 month. Withdrawal of betaine 250 mg/kg/d was also associated with a rise in plasma homocystine and a fall in methionine levels. Carnitine 100 mg/kg/d led to an increase in urinary excretion of propionylcarnitine, but did not affect plasma methylmalonate levels. No beneficial biochemical effect of follinic acid could be documented at a dose of 25 mg/d. Our results suggest that daily injections of OH-B12 are not necessary to maintain metabolic control and that orally administered OH-B12 is unlikely to be effective. Betaine appears to act synergistically with OH-B12 and should be part of the treatment regimen. Although there are theoretical reasons for using l-carnitine and folinic acid, we could not document their effectiveness in these two patients.
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U2 - 10.1016/S0022-3476(88)80114-8
DO - 10.1016/S0022-3476(88)80114-8
M3 - Article
C2 - 3257264
AN - SCOPUS:0023830785
SN - 0022-3476
VL - 112
SP - 32
EP - 39
JO - The Journal of pediatrics
JF - The Journal of pediatrics
IS - 1
ER -