Search

Lower than average concentrations of tyrosine could be a factor in the fetal damage produced by maternal phenylketonuria (PKU). Dietary supplementation with L-tyrosine has been inconsistent in these reported pregnancies. Consequently, we studied the response to supplementation with L-tyrosine in five maternal PKU pregnancies. Before supplementation the mean plasma tyrosine concentration during midpregnancy was only 34 [micro]mol/L compared with the expected value of 45 [micro]mol/L in the normal population. A single dose of 1.3 g L-tyrosine was sufficient to raise plasma tyrosine concentrations well above the recommended minimum concentration of 45 [micro]mol/L. The response was rapid and sustained over a 3-h study period in each subject and was associated with a markedly increased ratio of tyrosine to large neutral amino acids. These results indicate that the plasma tyrosine concentration can be increased to normal or above-normal values in maternal PKU pregnancies for a period of [is greater than or equal to] 3 h by supplementation of the diet with L-tyrosine. The high ratio of tyrosine to large neutral amino acids indicates that tyrosine might readily cross the placenta and provide sufficient tyrosine to the fetus to support normal protein and catecholamine synthesis in what otherwise might be a tyrosine-poor environment. Am J Clin Nutr 1998;67:473-6.

OBJECTIVE: The purpose of this study was to evaluate the efficacy of a phenylalanine-restricted diet in reducing fetal morbidity associated with maternal hyperphenylalaninemia in women of childbearing age with blood phenylalanine levels >240 [Mu] mol/L (>4 mg/dl) on an unrestricted diet. STUDY DESIGN: Two hundred thirteen pregnant women with hyperphenylalaninemia that resulted in 134 live births have been enrolled in the study. Outcome measures were subject to the [[Chi].sup.2] test, Fisher exact test, analysis of variance, t test, or Wilcoxon nonparametric test for analysis. RESULTS: Optimal fetal outcome appeared to occur when blood phenylalanine levels

Neuroblastoma is a childhood cancer of cells of the sympathetic nervous system. There has been significant improvement in the treatment of this cancer among children under the age of one year. At least half the children diagnosed before the age of one year are likely to survive five years or more. However, among those diagnosed over the age of one, only one in five children is likely to achieve long-term survival. One might assume, therefore, that efforts to detect this cancer among younger children, before the symptoms of the cancer become obvious, might yield significant improvements in the success of treatment. Neurons of the sympathetic nervous system utilize the neurotransmitter substance norepinephrine, a catecholamine. As many as 90 percent of neuroblastomas secrete excess catecholamines; the detection of these substances in the urine can therefore provide a useful early detection tool. But does early detection actually result in increased survival? The Japanese have used this method in an experimental study of early detection for more than 10 years. They have found an increased rate of neuroblastoma; this suggests that many neuroblastomas are being detected that, if left on their own, might have regressed and never achieved clinical importance. An excellent survival rate was reported for the children diagnosed by the early detection test, but the physiological characteristics of these children were all indicative of better chances for survival. This has raised suspicions that there might be two (or more) biological types of neuroblastoma. The earlier form might be intrinsically more curable, the later form more aggressive and dangerous. The early detection program may not, therefore, actually save lives. This program may detect more of the cases that have better survival features to begin with, and the more aggressive form may continue to make its destructive appearance after the age of one year in some patients. The principle of mass screening for early detection continues to be worthy of investigation. However, at present there is no evidence that justifies the effort and expense of mass screening; there is no evidence that such a program would save lives. (Consumer Summary produced by Reliance Medical Information, Inc.)

The case report is presented of an infant with homocystinuria (increased levels of homocysteine, an amino acid, in the urine). This condition results from a deficiency of the enzyme cystathionine beta-synthase (CBS), which normally catalyzes the manufacture of cystathionine from homocysteine. When CBS is deficient, levels of homocysteine and methionine (a product of homocysteine) build up. CBS deficiency is associated with mental retardation, abnormalities of the lens of the eye and of the bones, and blood clots that can lodge in arteries or veins. The infant described in the case report also had pancytopenia, a severe decrease in the numbers of all types of blood cells, and a deficiency of folate (commonly associated with blood cell deficiency). Treatment with folic acid, and the administration of a low-methionine diet with cysteine supplementation (the usual treatment for CBS deficiency), led to the normalization of the patient's high methionine levels and the resolution of many other symptoms. A discussion is presented of the infant screening processes that normally detect CBS deficiency; in this case, the patient probably had a genetically determined error of homocysteine metabolism as well as an acquired folate deficiency because he was fed boiled cow's milk instead of formula. The suggestion is made that infants or children with severe folate deficiency should be evaluated for CBS deficiency even if the reasons for their folate deficiency seem clear. (Consumer Summary produced by Reliance Medical Information, Inc.)

That was a great tribute to an amazing individual. I particularly liked your metaphor regarding his communications skills and Herculean tenacity! I can recall many meetings where he simply wore [...]

Phenylketonuria (PKU) is a genetic disease that results in an enzyme deficiency. The enzyme is necessary to convert phenylalanine, an amino acid, into tyrosine, another amino acid. The result of PKU is an accumulation of phenylalanine in the tissues. Mental retardation and neurologic disorders can result if PKU is not treated promptly after birth. Although much is known about PKU, the actual pathology of the disease as it affects the brain is not well understood. Reduction of myelin (the protective layer that surrounds nerves) is often found. Some studies have shown changes in the gray matter of the brain in PKU patients. This study examined the amount of loss of white matter myelination and gray matter changes in 15 patients with PKU, using magnetic resonance (MR) imaging. These results were compared with the extent of mental retardation resulting from PKU and the biochemical severity of the disease to see if a relationship existed between the findings of MR imaging and the severity of disease. MR results showed white matter abnormalities in the posterior part of the cerebrum but no white matter abnormalities in the brain stem, cerebellum or cortex. The abnormalities were found in the front part of the cerebrum in severe cases. There was no correlation between white matter abnormalities as detected by MR and IQ (intelligence quotient) score. No correlation was found between intelligence and atrophy of gray matter. These results indicate that MR imaging can be used to show the loss of myelination of white matter in patients with PKU. However, the extent of these losses does not correlate significantly with the clinical severity of the disease. (Consumer Summary produced by Reliance Medical Information, Inc.)

Phenylketonuria (PKU) is a birth defect in which the enzyme responsible for breaking down phenylalanine, an amino acid required for the growth of a fetus, is lacking. The phenylalanine builds up in the blood and deposits in the brain of affected fetuses. Infants born to mothers who were born with classic PKU are at risk for complications such as mental retardation, small head size, congenital heart disease and low birth weight. Women who have a blood phenylalanine of 1,200 micromoles per liter or more are highly likely to give birth to an affected fetus. In women with less severe disease, the risk is lower. Although a phenylalanine-free diet is effective in reducing the amount of circulating phenylalanine, some women remain untreated. Previous studies suggest that there might be a threshold level of 600 micromoles per liter, above which phenylalanine begins to affect the brain. A study of children born to untreated mothers with varying levels of PKU is reported. Intelligence tests were given to 24 eight-year-old children. The IQ scores were plotted against the mother's phenylalanine levels. Children born to mothers who had mild PKU (165 to 540) had children of normal or superior intelligence. Children born to mothers with atypical or severe PKU generally had lower intelligence scores. The scores did fall below normal until the blood level of phenylalanine rose above 600. It is not clear whether infants who are born to mothers with severe but treated PKU have physical reactions similar to the infants born to untreated mothers. (Consumer Summary produced by Reliance Medical Information, Inc.)

To the Editor: Gamma-hydroxybutyric acid (GHB), or 4-hydroxybutyric acid, is an endogenous neurochemical that is formed in the human brain from gamma-aminobutyric acid (GABA) metabolism (1). GHB's natural presence in [...]

Infants of mothers with phenylketonuria (PKU), an inborn error of metabolism, may develop microcephaly, an abnormal smallness of the head; mental retardation; and congenital heart defects. They also tend to have low birthweight. There is limited information about the development of abnormalities in children of fathers with PKU. One study showed that men with PKU had lower sperm counts and reduced semen volume, suggesting a limited reproductive potential. However, men with PKU are capable of fathering children, and these children have a lower frequency of abnormalities than children of mothers with PKU. Previous studies examining the outcome of children of fathers with PKU have produced inconsistent results. Six families of fathers with PKU are described and include nine offspring without PKU. The results suggest that paternal PKU does not adversely affect the outcome of offspring. None of the nine children had microcephaly, low birthweight, or congenital heart disease. In addition, the study showed that men with PKU have normal fertility. The greater frequency of abnormalities associated with maternal PKU may result from the transfer of biochemical abnormalities from the mother to the fetus during pregnancy, not from damage to the fertilized egg caused by genetic factors. (Consumer Summary produced by Reliance Medical Information, Inc.)