Congenital Methylmalonic Aciduria - Homocystinuria With Megaloblastic Anemia : Observations on Response to Hydroxocobalamin and on the Effect of Homocysteine and Methionine on the Deoxynridine Suppression Test
نویسنده
چکیده
Congenital methylmalonic aciduria-homocystinuria, a disorder with an incompletely defined cobalamin abnormality. has not been accompanied by megaloblastosis in most of the initially described cases. This has raised questions about the exact role of cobalamin in relation to megaloblastic anemia. Therefore, we present our observations on a patient with this syndrome whose manifestations conformed to current concepts of cobalamin function and on her response to hydroxocobalamin. In addition to the megaloblastic anemia (and other hematologic abnormalities) she developed severe neurologic impairment shortly after birth. Hydroxocobalamin injections diminished her methylmalonic acid and homocystine excretion and corrected her megaloblastosis. though mild neutrophil nuclear hypersegmentation has persisted even after a year. Clinical status also improved. particularly physical growth and neurologic development. However, she remains neurologically impaired following an unexplained clinical catastrophe. We documented her megaloblastic process by demonstrating abnormal deoxyuridine suppression test results in her initial bone marrow aspirate and normal results after treatment. Furthermore, the abnormal deoxyuridine suppression was corrected in vitro by folic acid, but not by methyltetrahydrofolic acid. cyanocobalamin. adenosylcobalamin. methylcobalamin, or methionine. Homocysteine slightly worsened the deoxyuridine suppression pattern. Subsequent studies showed that. in contrast to previous reports. homocysteine had no beneficial effect in other normoblastic or megaloblastic marrows either. The findings in our patient are compatible with the “methyltetrahydrofolate trap” hypothesis. Why this syndrome presents such a wide spectrum of manifestations is not entirely clear, nor is it clear why it should differ so from other disorders of cobalamin. These aspects are reviewed. Severity of the defect. differences in tissue susceptibility. or possibly even other factors such as ability to retain cobalamin intracellularly may influence the manifestations of this metabolic disorder.
منابع مشابه
Abnormal Deoxyuridine Suppression Test in Congenital Methylmalonic Aciduria-Homocystinuria Without Megaloblastic Anemia: Divergent Biochemical and Morphological Bone Marrow Manifestations of Disordered Cobalamin Metabolism in Man
We studied two brothers (J.R. and M.R.) with the cobalamin D variant of congenital methylmalonic aciduria-homocystinuria. whose previously reported lack of megaloblastic anemia conflicted with current concepts of cobalamin’s role in DNA synthesis and the “methyltetrahydrofolate (MTHF) trapS’ hypothesis. Both subjects were indeed hematologically normal. although JR. had a mean corpuscular volume...
متن کاملAbnormal Deoxyuridine Suppression Test in Congenital Methylmalonic Aciduria-Homocystinuria Without Megaloblastic Anemia: Divergent Biochemical and Morphological Bone Marrow Manifestations of Disordered Cobalamin Metabolism in Man
We studied two brothers (J.R. and M.R.) with the cobalamin D variant of congenital methylmalonic aciduria-homocystinuria. whose previously reported lack of megaloblastic anemia conflicted with current concepts of cobalamin’s role in DNA synthesis and the “methyltetrahydrofolate (MTHF) trapS’ hypothesis. Both subjects were indeed hematologically normal. although JR. had a mean corpuscular volume...
متن کاملAbnormal Deoxyuridine Suppression Test in Congenital Methylmalonic Aciduria-Homocystinuria Without Megaloblastic Anemia: Divergent Biochemical and Morphological Bone Marrow Manifestations of Disordered Cobalamin Metabolism in Man
We studied two brothers (J.R. and M.R.) with the cobalamin D variant of congenital methylmalonic aciduria-homocystinuria. whose previously reported lack of megaloblastic anemia conflicted with current concepts of cobalamin’s role in DNA synthesis and the “methyltetrahydrofolate (MTHF) trapS’ hypothesis. Both subjects were indeed hematologically normal. although JR. had a mean corpuscular volume...
متن کاملcobalamin metabolism in man biochemical and morphological bone marrow manifestations of disordered aciduria-homocystinuria without megaloblastic anemia: divergent Abnormal deoxyuridine suppression test in congenital methylmalonic
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متن کاملVitamin B12-responsive neonatal megaloblastic anemia and homocystinuria with associated reduced methionine synthase activity.
We present findings on an infant with neonatal megaloblastic anemia, homocystinuria, and neurologic dysfunction that included developmental delay and tonic seizures. There was no methylmalonic aciduria. Cyanocobalamin therapy was accompanied by complete hematologic and neurologic recovery, diminished homocystine excretion, and subsequently normal neurologic development. Cultured fibroblasts and...
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تاریخ انتشار 2005