Folic acid administration to women in the periconceptional period reduces the occurrence of neural tube defects (NTDs) in their offspring. A polymorphism in the gene encoding methylenetetrahydrofolate reductase (MTHFR), 677C-->T, is the first genetic risk factor for NTDs in man identified at the molecular level. The gene encoding another folate-dependent enzyme, methionine synthase (MTR), has recently been cloned and a common variant, 2756A-->G, has been identified. We assessed genotypes and folate status in 56 patients with spina bifida, 62 mothers of patients, 97 children without NTDs (controls), and 90 mothers of controls, to determine the impact of these factors on NTD risk. Twenty percent of cases and 18% of case mothers were homozygous for the MTHFR polymorphism, compared to 11% of controls and 11% of control mothers, indicating that the mutant genotype conferred an increased risk for NTDs. The risk was further increased if both mother and child had this genotype. The MTR polymorphism was associated with a decreased O.R. (O.R.); none of the cases and only 10% of controls were homozygous for this variant. Red blood cell (RBC) folate was lower in cases and in case mothers, compared to their respective controls. Having a RBC folate in the lowest quartile of the control distribution was associated with an O.R. of 2.56 (95% CI 1.28-5.13) for being a case and of 3.05 (95% CI 1.54-6.03) for being a case mother. The combination of homozygous mutant MTHFR genotype and RBC folate in the lowest quartile conferred an O.R. for being a NTD case of 13.43 (CI 2.49-72.33) and an O.R. for having a child with NTD of 3.28 (CI 0.84-12.85). We propose that the genetic-nutrient interaction--MTHFR polymorphism and low folate status--is associated with a greater risk for NTDs than either variable alone.

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To evaluate the role of ultrasonography in the investigation of childhood urinary tract infections (UTI), 240 patients aged 2 days to 15 years with a first-documented UTI were examined first by sonography, then by intravenous urography (IVU), and when indicated by voiding cysto-urethrogram (VCU). According to the results of these examinations, the patients were divided into three groups. In Group 1 (71 patients), abnormal sonographic findings were confirmed by the radiographic studies. Patients in Group 2 (51 patients) had discrepancies between sonographic and radiographic findings, the most important of which concerned the assessment of vesico-ureteric reflux (VUR). In Group 3 (118 patients), sonographic and subsequent radiographic investigations were normal. Although ultrasonography can sometimes detect VUR, major reflux can be missed by sonography alone. In young children at risk for reflux nephropathy, ultrasound examination of the urinary tract must be accompanied by a VCU or isotope cysto-urethrogram.