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Many genetic disorders result from an inborn error of metabolism. The patient lacks an important enzyme, and as a result critical biochemical reactions cannot take place. Some inborn errors of metabolism are quite common, but a deficiency in the enzyme 5,10-methylenetetrahydrofolate reductase is rare. The enzymatic defect results in the presence of large amounts of the amino acid homocysteine in the urine, a condition called homocystinuria. Although the condition is rare, it is quite serious. The mental development is retarded from early infancy and death often comes within a year. Three unusual patients have now been found, which suggests that the disorder may go unrecognized. All three patients were young adults in their early 20s when they had severe strokes. Investigation revealed that all three patients were retarded, but only mildly so. Imaging studies revealed abnormalities in all three patients and brain atrophy in two. The three patients were all from the same family, and a thorough biochemical analysis was performed revealing excessive homocysteine in the urine. The three patients were among six siblings in the family, and further investigation revealed that one additional sibling had no symptoms but nevertheless had high levels of homocysteine in her urine. Two of the three patients died within one year of diagnosis. These cases illustrate that homocystinuria need not always result in rapid death in infancy. Furthermore, the cases suggest that the enzymatic defect may contribute to blood vessel abnormalities, which lead to recurrent strokes in young adulthood. (Consumer Summary produced by Reliance Medical Information, Inc.)

Absorption of cobalamin free or bound to chicken serum was assessed in nine patients with pancreatic insufficiency. Simultaneously the in vitro effect of duodenal juice collected from six patients and seven controls was tested on labelled cobalamin complexed to chicken serum or to R salivary binder. Malabsorption of free cobalamin was observed in one of nine patients and in four of nine patients when cobalamin was administered bound to chicken serum. The in vitro effect of duodenal juice on cobalamin complexed to chicken serum or to R salivary binder was studied: the percentage of free cobalamin released was significantly decreased in pancreatic insufficiency compared with controls whatever the binder used; the degradation of R salivary binder was different in pancreatic insufficiency and in controls. Despite the in vitro abnormalities observed in pancreatic insufficiency, these did not correlate with the in vivo absorption of cobalamin which was often normal in our patients. [ABSTRACT FROM PUBLISHER]

1. A pharmacokinetic study of the natural (−)−isomer of folinic acid ((−)−5 CHOTHF) and of total (−)−folates was performed in 12 healthy subjects after i.v. and oral administration of the racemic form of folinic acid. 2. After a 25 mg i.v. injection, (−)−5 CHOTHF kinetics were described by a biexponential function. The mean steady state volume of distribution (Vss) was 161; systemic and renal clearances averaged 335 and 53 ml min-1, respectively. After the same oral dose, (−)−5 CHOTHF was rapidly absorbed. Plasma concentrations of unchanged drug were much lower than those achieved after i.v. administration but in nine subjects, the disposition kinetics were also biexponential. Absolute bioavailability was only 4% as a consequence of a significant intestinal first pass effect. 3. AUC and t1/2Z values for total (−)− folates were similar after both routes of administration, indicating that the drug was fully absorbed. However the AUC of the active metabolite after i.v. dosage was only half that after oral dosage. 4. The amounts of total (−)−folates excreted in urine after both routes of administration were not significantly different and averaged one third of the dose after 24 h, whereas excretion of (−)−5 CHOTHF was three times less after oral treatment than after parenteral treatment. 5. Oral administration is a more suitable route for folinic acid therapy because more of the active metabolite is produced than after parenteral injection. [ABSTRACT FROM AUTHOR]

Serum, red cell and squame folate content have been measured in fifty cases of psoriasis with extensive lesions. Reduced serum and red cell folate have been found in 44% of the patients. Folic aid absorption, studied in twenty-six patients, was impaired in four and significantly increased in all the others. Squame folate content has been found too low to explain the folate deficiency. Malabsorption is a possible hypothesis but it occurs too rarely (four cases). The most likely explanation of folate deficiency seems to be an increased utilization of folate by the skin epidermal cells as a result of the rapid turnover rate. The increased absorption found in most cases investigated could be a compensatory mechanism to equilibrate folate balance. [ABSTRACT FROM AUTHOR]