Homocystinuria and Megaloblastic Anemia Responsive to Vitamin B₁₂Therapy

Abstract

We describe an inborn error of vitamin B12 metabolism in an infant who had severe developmental delay, megaloblastic anemia, and homocystinuria. There was no evidence of methylmalonic aciduria or deficiency of folate or vitamin B12. Treatment with hydroxocobalamin, but not with cyanocobalamin and folic acid, resulted in rapid clinical and biochemical improvement. Cultured fibroblasts showed an absolute growth requirement for methionine, defective incorporation of radioactivity from [14C]5-methyltetrahydrofolate into protein, and normal incorporation of radioactivity from [14C]propionate, thus assigning the intracellular defect to methionine synthesis. The proportion of intracellular methylcobalamin in the fibroblasts was decreased, but that of 5'-deoxyadenosylcobalamin was normal. Methionine synthetase activity in cell extracts was normal, as was cobalamin incorporation into cultured cells. This defect differs from those described previously in being limited to methylcobalamin accumulation and defective use of 5-methyltetrahydrofolate by intact cells with normal activity of methylmalonyl CoA mutase.

Purification of Soluble Cytochrome b 5 as a Component of the Reductive Activation of Porcine Methionine Synthase

“…2). This is strongly supported by the existence of the cblE class of patients with an inborn error of cobalamin metabolism resulting in a functional methionine synthase deficiency, albeit the methionine synthase itself is apparently normal (13)(14)(15). Biochemical analysis of fibroblast cells from cblE patients indicates that the reductive activation system is compromised.…”

Cloning and mapping of a cDNA for methionine synthase reductase, a flavoprotein defective in patients with homocystinuria

“…For a second class of patients, belonging to a distinct complementation group, cblE, net methionine synthase activity appears reduced. Their defect is in a reducing system required for maintenance of the enzyme in a functional state (7,12,13).…”

Screening Newborns for Multiple Organic Acidurias in Dried Filter Paper Urine Samples: Method Development

“…Therapy for all conditions is available and has been effective to a variable degree. In vitamin deficiency states or in vitamin-dependent inherited defects, administration of the specific vitamin or its derivative resulted in marked improvement or complete recovery ( I 7-2 1, [23][24][25][26][27]. Other nonvitamin-dependent organic acidurias have been treated with dietary manipulations, administration of natural nutlitional factors, and medicatlons (28,29).…”