CONGENITAL DEFECT IN INTRACELLULAR COBALAMIN METABOLISM RESULTING IN HOMOCYSTINURIA AND METHYLMALONIC ACIDURIA .1. CASE-REPORT AND HISTO-PATHOLOGY

Abstract

The case is described of an infant who suffered from progressive, severe dystrophy, hemolytic and megaloblastic anemia, hematuria, proteinuria and slight uremia. He died at 4 mo. of age, following 2 acute episodes of heart failure. Abnormally increased excretion of methylmalonate and homocystine was detected by a screening program for metabolic disorders. Amino acid analyses showed that the plasma and urine levels of methionine were very low, whereas those of cystathionine were raised. Vitamin B12 deficiency, malabsorption or abnormal cobalamin transport were excluded by a normal serum total cobalamin and normal transcobalamins. A congenital error of cobalamin metabolism was suggested. Treatment with vitamin B12 resulted in a biochemical though not a clinical response. Postmortem examination revealed severe vascular lesions with changes in the kidney characteristic of thrombotic microangiopathy supporting a diagnosis of hemolytic-uremic syndrome. The elevated plasma homocysteine apparently induced the vascular lesions by causing detachment of endothelium.