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THE introduction of mass screening programs for the detection of inborn errors of metabolism1 almost inevitably reveals a variety of new artefacts which those who deal with these diseases must learn to recognize. We describe here one of these artefacts: D-methioninuria due to ingestion of Dl-methionine-fortified infant formula. REPORT OF A CASE The patient, the second-born of male dizygotic twins delivered in a hospital in a nearby community at 32 weeks' gestation, weighed 1,814 gm (4 lb) at birth. His brother weighed 1,561 gm (3 lb 7 ounces). The mother, a primipara, was convalescing from viral hepatitis complicated by myocarditis when spontaneous labor began. The infant spent the first three days in an incubator."Very foul stools" were noted at 4 days of age, and this was more or less persistent throughout his nursery course. After initial 5% dextrose feedings, the infant was given a cow's milk formula, and

HYPERMETHIONINEMIA in infancy occurs regularly with homocystinuria due to cystathionine synthase deficiency.1,2 It has also been seen in association with hereditary tyrosinemia3 and with neonatal hepatitis.4 Interest in the early detection of hypermethioninemia has been stimulated by the fact that homocystinuria due to cystathionine synthase deficiency is one of the more common inborn errors of amino acid metabolism and by the possibility that brain damage in this condition may be prevented by a special low-methionine diet.1In 1966 the Massachusetts Metabolic Screening Program conducted by the State Laboratory Institute, Massachusetts Department of Public Health, incorporated blood filter paper chromatography for the detection of hypermethioninemia and other hyperaminoacidemias in newborn and 4- to 10-week-old infants.5,6 In January 1968, the Guthrie bacterial inhibition assay for methionine (R. Guthrie, unpublished data) was included as a standard test for all blood specimens received in the Massachusetts screening program. These

Mentally retarded non-phenylketonuric offspring from untreated phenylketonuric mothers have been reported upon by a number of groups. To this list we add some additional cases. These offspring commonly have lower I.Q's than their mothers. It is reasonable to postulate that the high concentrations of phenylalanine or its metabolites in the blood of the untreated mother, which is actively transported across the placenta into the blood of the infant, is the cause of the frequently severe damage to the vulnerable infant brain in utero. The fact that artificially produced high concentrations of phenylalanine in the blood of pregnant monkeys and of pregnant rats seems to have culminated in offspring with impaired learning abilities is consistent with this supposition. The results indicating apparently normal mental development, so far, in the nonphenylketonuric offspring of at least 2 phenylketonuric mothers treated with low phenylalanine diets during pregnancy, are encouraging. Because of the advent of routine screening tests for PKU in the newborn, there are an increasing number of phenylketonuric girls, treated in their early years but now on a normal diet, who are approaching the childbearing period and who are mentally normal. Consequently, there is a growing opportunity and responsibility for preventing mental retardation in their future nonphenylketonuric children. It is suggested that dietary treatment during the pregnancies of phenylketonuric mothers be seriously considered, with caution exercised so that the blood concentrations of phenylalanine in the mother under treatment be maintained above 3 but below 8 mg. per 100 ml. Routine urine testing for PKU is, therefore, recommended for all women at the first prenatal visit and at the premarital examination.

Transient tyrosinemia has been found in approximately 1.8% of all infants in Massachusetts tested within the first 6 weeks of life (2,085 infants out of a total screened population of 117,752). About 24% have been full-term by weight and gestational criteria. In general, infants with lower birth weights had more marked tyrosinemia. However, several babies with average or above average birth weights had blood tyrosine concentrations of 10 mg/100 ml to more than 20 mg/100 ml, and in a few of these latter infants the tyrosinemia lasted as long as 9 to 13 weeks after birth. The infants have been clinically well.

The conclusions which must be drawn from the data on early detection of phenylketonuria (PKU) reported by Berry et al in The Journal of Aug 24, 1964 (189:641), are different from those reported by Allen and Wilson in The Journal of May 25, 1964 (188:720). On the basis of three phenylketonuric patients who had positive ferric chloride tests in the first eight days of life (and seven others aged 17 to 54 days with positive tests) Allen challenged the accepted view that the ferric chloride test is not of great value in early infancy. An editorial in The Journal (188:748 [May 25] 1964) commenting on Allen's paper stated, "It is recommended that a positive blood test should always be followed by a urine test, and treatment should not be initiated until the urine test becomes positive...."Berry et al tested 17 newborn sibs of known phenylketonurics. Of