Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0018799 (heart disease)
 34,133 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Two sisters were diagnosed as having phenylketonuria at the age of 13 years and eight years and having Wechsler IQs of 48-58 and 71-81 respectively. Neither girl was treated with diet. At the age of 21 years the older girl became pregnant. Her blood phenylalanine level was 23mg/100 ml. A low phenylalanine diet, instituted from the 10th week of gestation, maintained her blood phenylalanine levels below 6mg/100ml for the rest of the pregnancy. A female baby, of birth weight 3216g and normal skull size, was delivered at term. The baby died at 14 days of congenital heart disease. Pregnancy in a phenylketonuric woman carries high risks to the fetus. A generation of treated phenylketonuric girls is approaching reproductive life, and doctors and the girls themselves need to be alerted to these risks and the need for strict dietary control during pregnancy. There are probably unrecognised women in the community with phenylketonuria or with hyperphenylalaninaemia whose babies face similar risks. Identification of these women could be achieved by antenatal Guthrie testing.
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PMID:Progeny, pregnancy and phenylketonuria. 105 68

Maternal PKU is an embryo-fetopathy caused by elevated plasmaphenylalanine levels in pregnant women with hyperphenylalaninemia and phenylketonuira. Leading symptoms are microcephaly, mental retardatioin and congenital malformations, especially congenital heart disease. Maternal PKU becomes more important since early treated and normally developed girls with PKU are reaching their reproductive age in increasing numbers. There is a lack of adequate knowledge about the dangers of maternal PKU in at-risk women. Only 43% of these women in the Federal Republic of Germany are located by now and can be informed and instructed. Ways and conditions of tracking are described.
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PMID:[Maternal phenylketonuria. Problems in detecting and risk educating identified females]. 156 7

Cells from a particular portion of the cranial neural crest (cardiac neural crest) migrate from the neural fold into pharyngeal arches 3, 4 and 6, where they provide the support for the endothelium of the aortic arch arteries, and by migration into the outflow tract become involved in septation of the truncus arteriosus. Ablation of the premigratory cardiac neural crest results in persistent truncus arteriosus and other defects reminiscent of the DiGeorge syndrome in man. Removal of a small area of the cardiac neural crest causes a spectrum of heart defects classified together as dextraposed aorta including changes like that of Fallot's tetralogy in man. Some inflow tract anomalies have also been found. Pilot studies injecting phenylalanine into developing chick embryos at a very early stage had little effect on embryo viability or on the incidence of congenital heart defects. However, sham-treated animals produced predominantly small simple ventricular septal defects but phenylalanine-treated embryos had more serious and complex heart anomalies. It is not possible to say yet that congenital heart disease in the offspring of mothers with untreated phenylketonuria is due to phenylalanine-induced damage to the neural crest, but the pilot studies in chick suggest that this idea is worth pursuing.
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PMID:The effects of high phenylalanine concentration on chick embryonic development. 212 26

Fetal echocardiography is a well-established technique for the prenatal identification of congenital heart disease. One of the indications for its use is the presence of extracardiac anomalies, as such coexistent defects may have important implications for obstetric and neonatal management. We have reviewed the obstetric and pediatric literature to examine reported associations. If a fetus is suspected to have hydrocephalus, microcephaly, holoprosencephaly, agenesis of the corpus callosum, Meckel-Gruber syndrome, esophageal atresia, duodenal atresia, diaphragmatic hernia, omphalocele, or renal dysplasia, cardiac evaluation should be pursued. Furthermore, echocardiography may be of help in differential diagnosis of some anomalies (for instance, skeletal dysplasias). Maternal diabetes and phenylketonuria, as well as exposure to phenytoin, trimethadione, or isotretinoin, may result in multiple systemic defects, including congenital heart disease.
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PMID:Congenital heart disease and extracardiac anomalies: associations and indications for fetal echocardiography. 293 23

Pregnant rats were loaded with L-phenylalanine, and the distributions of [14C]leucine and [14C]urea into fetal plasma and tissues were examined. Uptake of [14C]leucine into the supernatant and protein fractions of fetal plasma and tissues was low in the rats loaded with phenylalanine. In contrast, [14C]urea was distributed identically in both groups, indicating that maternal hyperphenylalaninemia did not affect blood flow across the placenta. Administration of phenylalanine and p-chlorophenylalanine produced amino acid imbalance in fetal tissues. Along with these changes, polysomes of the affected fetal heart and brain disaggregated without changes in the ribonuclease activity. These results indicate that high phenylalanine levels in maternal plasma disturb the active transport of amino acids across the placenta, causing an amino acid imbalance and disaggregation of polysomes in fetal heart and brain. These changes may contribute to the congenital heart disease and mental retardation of maternal phenylketonuria.
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PMID:Effects of phenylalanine loading on protein synthesis in the fetal heart and brain of rat: an experimental approach to maternal phenylketonuria. 294 18

Maternal phenylketonuria (PKU) refers to fetal damage from PKU in the pregnant woman. The progeny from such pregnancies are almost always microcephalic and mentally subnormal and have an increased frequency of congenital heart disease and low birth weight. Treatment with a phenylalanine-restricted diet, if begun before conception, seems to protect the fetus. The degree of protection is much less if dietary treatment is delayed until the pregnancy is in progress. The origin of fetal damage in maternal PKU is not known. Due to placental concentration of amino acids, the fetus is exposed to a higher concentration of phenylalanine than that in the mother, but it is not certain that phenylalanine is the toxic agent. Animal models made hyperphenylalaninemic by the administration of phenylalanine, often accompanied by a phenylalanine hydroxylase inhibitor, do not reproduce the full maternal PKU syndrome; but fetuses and newborns from these models have had reduced growth of the body and brain, and offspring later may show evidence of impaired learning ability.
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PMID:Maternal phenylketonuria. Review with emphasis on pathogenesis. 332 36

Dietary management of five pregnancies in two women (sisters) with classical phenylketonuria (PKU) is described. One child died neonatally of congenital heart disease and one pregnancy miscarried. Of the three surviving children the only physically and mentally normal child, followed up to eight years, was born after a carefully planned pregnancy with strict dietary control preconceptually and throughout pregnancy. One pregnancy treated dietetically from six weeks gestation resulted in a child mentally normal at seven years but born with oesophageal atresia. The third surviving child is microcephalic and mentally retarded but dietetic treatment did not commence till 28 weeks gestation. It is concluded that to be effective, dietary control must be instituted preconceptually.
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PMID:Women with phenylketonuria: successful management of pregnancy and implications. 385 60

Untreated maternal phenylketonuria (PKU) may result in nonphenylketonuric offspring with mental retardation, microcephaly, congenital heart disease, and low birth weight. We obtained information about 34 pregnancies in which dietary therapy was instituted to lower the concentration of phenylalanine in maternal blood in an attempt to avoid fetal damage. The outcomes varied from mental normality with no evidence of fetal effect to neonatal death due to congenital heart disease. Dietary therapy with control of the maternal biochemical abnormalities is not yet of proved efficacy in preventing these fetal effects. The available data tend to support initiation of dietary therapy prior to conception for best results, but the number of cases is small and points to the need for further research.
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PMID:Maternal phenylketonuria--results of dietary therapy. 705 57

Since many women with phenylketonuria (PKU) will have children of their own, we were interested in ascertaining the effect of maternal PKU and hyperphenylalaninemia on the offspring of such women. We reviewed the literature on this subject and obtained additional unpublished data through an international survey. Data were collected on 524 pregnancies in 155 women; in 34 pregnancies a low-phenylalanine diet was begun after or shortly before pregnancy was established. Among untreated pregnancies, the frequencies of mental retardation, microcephaly, and congenital heart disease were greatly increased over those in the normal population, and these increases correlated with the mother's blood levels of phenylalanine. Ninety-five per cent of mothers with blood phenylalanine concentrations of 20 mg per deciliter or higher had at least one mentally retarded child. Bias introduced by case-finding methods cannot explain these results. It is not clear from our review whether dietary treatment begun after conception is helpful, but treatment begun before conception should be evaluated.
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PMID:Maternal phenylketonuria and hyperphenylalaninemia. An international survey of the outcome of untreated and treated pregnancies. 742 47

MPKU pregnancies, with or without dietary treatment to reduce maternal plasma phenylalanine (phe), show variable, increased non-physiologic levels, as the putative cause of fetal teratogenicity. Cerebral dysgenesis with clinical neonatal microcephaly and congenital heart disease indicates altered organ morphogenesis. Although there is not an established precise relationship between maternal phe levels and outcome, dietary restriction before or early in gestation is universally advised. Both human experience and animal research have suggested differential organ responses to high and low phe levels. Structural microencephaly may be due to reduced brain volume or abnormal regional brain development. Infants in MPKU are also at risk to develop PKU. Microencephaly was evident by MRI in 8 of 21 infants born to 12 MPKU mothers; 2 infants of one mother developed PKU. All levels of gestational plasma phe were associated with otherwise structurally normal infant microencephalic brains appropriate for age in myelination. CHD occurred in one microencephalic infant of a classic MPKU treated in the first trimester. Maternal, cord and neonatal plasma phenylalanine at delivery did not correlate with teratogenic effects. Only untreated 'classic' MPKU fetal effects appear predictable.
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PMID:MRI characterization of cerebral dysgenesis in maternal PKU. 776 67


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