1. Rats were deprived of dietary folate for 12 and 9.5 months in two experiments; one with and one without succinylsulfathiazole added to the diet. Folate levels decreased faster in the former experiment and the final blood values were lower. Tissue folate was examined in the latter experiment only. 2. The animals were repeatedly examined with neurological tests and compared with a control group supplemented with folic acid. Every test proved normal. Measurement of motor nerve conduction velocities after 12 months in the experiment where succinylsulfathiazole was given revealed lower velocities in the non-supplemented group. There was no difference between the groups in the experiment without succinylsulfathiazole. 3. In the latter experiment brain folate was reduced by only 16% in the non-supplemented animals compared with the controls, whereas whole blood folate fell by 60%, liver folate by 50% and sciatic nerve folate by 59%. 4. The central nervous system is resistant to systemic folate depletion, whereas the peripheral nerves are depleted to the same degree as the extra-neural tissues.
Methylmalonic acidemia (8) or aciduria (5) is a newly described inborn error of metabolism. Clinically, the disease is characterized by metabolic acidosis, vomiting, dehydration, muscular hypotonia, and retarded psychomotor development. Life-threatening crises of acidosis may develop during the course of even mild acute infections or during periods of high protein intake (3). The main biochemical features are methylmalonic acidemia, high urinary excretion of methylmalonic acid and intermittent ketosis.The accumulation of methylmalonic acid is caused by a block in the two-step conversion of methylmalonyl-CoA to succinyl-CoA (4, 6, 7). In the first step the enzyme methylmalonyl-CoA racemase (EC 5.1.99.1) catalyzes the reversible conversion of D-methylmalonyl-CoA to L-methylmalonyl-CoA, and in the second step methylmalonyl-CoA mutase (EC 5.4.99.2) catalyzes the reversible conversion of L-methylmalonyl-CoA to succinyl-CoA. The last enzyme has cobamide coenzyme as a co-factor.The metabolic block in methylmalonic acidemia may thus be explained by a deficiency of one or both of the two enzymes. Since patients with pernicious anemia are This work has been supported by a grant from the Swedish Medical Research Council (2583). Acta Pcediat Scand 58known to excrete up to 1 g of methylmalonic acid in the urine per day (1, 2) the possibility exists that there is, in methylmalonic acidemia, an abnormally high requirement of cobamide coenzyme, i.e. a so-called dependency condition. In order to test the validity of this hypothesis, the metabolic effect of a large dose of cobamide coenzyme has been studied in two patients with methylmalonic acidemia.The first patient (case E. B.) is a girl of 2 9/12 years of age, and whose clinical history has been reported in detail previously (3). The second patient (case S. B.) is a 2-year-old boy with a history of mild to moderate attacks of metabolic acidosis sinct the neonatal period. When 1 7/12 years of age he got an acute upper respiratory tract infection and during the course of this disease he developed a severe ketosis and a pronounced metabolic acidosis and went into shock. Following intensive medical treatment, including the administration of large doses of sodium bicarbonate, he recovered from the acute episode. However, when the protein intake was increased after another week, the patient relapsed. Since it was then found that the urinary excretion of methylmaIonic acid ranged between 3 and 4 g per day and that the serum concentration of this compound was 23 mg per 100 ml, he was diagnosed as a case of methylmalonic acidemia. When the patient had recovered from the second severe attack of acidosis he was put on a low protein diet providing him with 2 g of protein per kg body weight per day. Since then he has been free of severe attacks of acidosis although he has continued to excrete large quantities of ketone bodies in the urine. There has never been any symptoms of vitamin B12 deficiency and the serum concentration of vitamin BE has been found to be 690 pg per ml.
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