Around 6% of infants born to mothers taking anticonvulsants have malformations, including neural tube defects, and a further proportion show developmental delay in later childhood. Three commonly used anticonvulsants, carbamazepine, phenytoin and sodium valproate, interfere with folic acid metabolism. We investigated the common 677 C>T mutation in the methylenetetrahydrofolate reductase (MTHFR) gene in samples from 57 patients and their parents and 152 controls to determine its contribution to the risk of fetal anticonvulsant syndrome. The 677 C>T mutation frequency was significantly higher in the mothers than in the controls, but there was no significant difference in 677 C>T frequency in the patients or in the fathers. Genotype frequencies in the mothers were significantly different from controls, there being an excess of 677 C>T homozygotes. Amongst the patients, there was an apparent excess of heterozygotes (not statistically significant), and the fathers were not significantly different from controls. Mutation in the MTHFR gene in a mother taking sodium valproate, phenytoin or carbamazepine during pregnancy is associated with fetal anticonvulsant syndrome in her offspring. The skewed distribution of genotypes in the affected children probably reflects the association of fetal anticonvulsant syndrome with the maternal genotype.

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values in the premenstrual phase may result in symptoms of water retention. Treatment should, therefore, be aimed at preventing both the natriuretic effect of progesterone in the postovulatory phase and the sodium-retaining and waterretaining effects of aldosterone in the premenstrual phase. ReferencesTonks CM. Premenstrual tension. Br J Psychiatry 1975;Special Number 9:399-408. 2 O'Brien PMS, Craven DJ, Selby C, Symonds EM. Treatment of premenstrual syndrome by spironolactone. BrJ Obstet Gynaecol 1979;86: 142-7. 3Ghose K, Coppen A. Bromocriptine and premenstrual syndrome: controlled study. Br Medj7 1977;i:147-8. 4 Dalton K. The premenstrual syndrome and progesterone therapy. London:Heinemann Medical Books, 1977.Backstrom T, Mattson B. Correlation of symptoms in premenstrual tension to oestrogen and progesterone concentrations in blood plasma. Case reportsWe studied three obese patients, all of whom underwent prolonged total therapeutic starvation resulting in pronounced, progressive weight reduction. During the fast all received supplements of potassium (as Slow K), allopurinol (300 mg/day), folic acid, and vitamins A, B, C, and D (as Multivite). One patient (case 1) also received oral iron treatment. Throughout the period of starvation all patients maintained normal serum vitamin B12 and iron concentrations.Case 1-A 23-year-old woman weighing 134 kg underwent a three-month fast. Before starting the fast her white blood cell count was normal (6-8 x 109/1) but fell as low as 3-5 x 109/1 (neutrophil count of 1-7 x 109/1) when allopurinol was started. On refeeding the patient continued to receive allopurinol for a further month and a minimal neutropenia persisted (2-4 x 109/1). When allopurinol was withdrawn the neutrophil count returned to normal. Sternal marrow biopsy performed during the fast showed normal maturation of the granulopoietic series but rather scanty numbers of polymorphs and precursors.Case 2-A 20-year-old man weighing 113 kg had a white cell count of 8-3 x 10'/1 before fasting. Neutropenia (neutrophils 1-7 x 109/1, total white cell count 3-6 x 109/1) developed after 34 days' starvation. Allopurinol was withdrawn and the white -cell and neutrophil counts returned to normal (white blood cell count 5-8 x 109/1) after three weeks. Case 3-A 19-year-old man weighing 130 kg had a white blood cell count of 8 5 x 109/1 before therapeutic starvation started. After four weeks of total fasting and treatment with allopurinol he developed leucopenia (3 9 x 109/1), which persisted until the end of the fast. The lowest neutrophil count recorded was 1-3 x 109/1. Allopurinol was continued for nine days of refeeding, during which time the neutropenia persisted. Thereafter the drug was withdrawn and his neutrophil count returned to normal after two days. CommentNeutropenia has often been observed during total therapeutic starvation and is known to occur in starving patients who have never received allopurinol. Hypotheses to explain its appearance during fasting have included the effects of protein deficien...