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Neuropediatrics 1986; 17(2): 94-99
DOI: 10.1055/s-2008-1052508
© Georg Thieme Verlag KG Stuttgart · New York

A Cobalamin Metabolic Defect with Homocystinuria, Methylmalonic Aciduria and Macrocytic Anemia*

R. J. Mamlok1 , J. N. Isenberg1 , D. K. Rassin1 , K.  Norcross2 , H. H. Tallan3
  • 1Department of Pediatrics, The University of Texas Medical Branch at Galveston, TX 77550, USA
  • 2Department of Neurology, The University of Texas Medical Branch at Galveston, TX 77550, USA
  • 3The New York State Institute for Basic Research in Developmental Disabilities, Staten Island, New York 10314, USA
* Supported by a Grant (RR-73) from the General Clinical Research Centers Program of the Division of Research Resources, National Institutes of Health. Presented in part at the Southern Society for Pediatric Research, New Orleans, LA, January, 1984 and the Society for Pediatric Research, San Francisco, CA, May, 1984.
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Publication History

Publication Date:
19 March 2008 (online)

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Abstract

We have identified a patient with methylmalonic aciduria and homocystinuria due to a defect in cobalamin metabolism of the cb1C type mutant. At the time of admission at eight months of age the patient was malnourished, hypotonic and had macrocytic anemia. Neonatal screening for hypermethioninemia associated with homocystinuria had been normal. Serum vitamin B12 was markedly increased and folate concentration was above normal, as were urinary homocystine and methylmalonic acid. The patient had abnormal brain stem auditory and visual evoked potentials. Fibroblast activity of N5-methyltetrahydrofolate: homocysteine methyltransferase was reduced to approximately 10% of concurrent controls. A course of therapy with hydroxocobalamin resulted in a 90% reduction in excretion of methylmalonic acid and normalization of the evoked potentials. These studies support the efficacy of hydroxocobalamin therapy in this disease, suggest that methylmalonic acid may be the most appropriate metabolite to monitor for therapeutic response, and indicate the importance of electrophysiologic studies in characterizing and in objectively monitoring the response to treatment of this metabolic disease.

Key words

Homocystinuria - Methylmalonic Aciduria - Cobalamin - Hydroxocobalamin - Evoked Potentials

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