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D Lobbregt

Publications and source records attributed to D Lobbregt.

8 recordsLinked to original sources
PubMed1998

Tyrosine supplementation in the treatment of maternal phenylketonuria.

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 micromol/L compared with the expected value of 45 micromol/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 micromol/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 > or = 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.

Female↗
PubMed1996

Fetal ultrasonography in maternal PKU.

Maternal phenylketonuria (PKU) is teratogenic and results in birth defects that include microcephaly, mental retardation, congenital heart disease, and intrauterine growth retardation. Treatment with a low phenylalanine diet can prevent or reduce the severity of the complications. Optimal benefit, however, requires frequent monitoring with fetal ultrasonography as a critical element. We have studied ultrasonography in 39 pregnancies enrolled in the Maternal PKU Collaborative Study and followed at our centre. First-trimester examinations in 24 pregnancies resulted in the discovery of non-viability in five. In each, this led to discontinuation of the difficult and expensive diet. Among the 33 pregnancies with second-trimester evaluation, congenital heart disease was identified in five. Two of these pregnancies were terminated. Microcephaly as determined by biparietal diameter (BPD) was identified in the second trimester in only one of nine fetuses who had microcephaly at birth. Among 20 pregnancies with third-trimester ultrasound, fetal microcephaly was identified by BPD in three of seven who had birth microcephaly. We conclude that fetal ultrasonography in maternal PKU is valuable during the first trimester in identifying non-viable pregnancies and determining gestational age and is also valuable during the second trimester in identifying congenital heart disease and perhaps other major anomalies, but not in identifying fetal microcephaly. Third-trimester ultrasound seems to be of limited usefulness.

Female↗
PubMed1996

Maternal non-phenylketonuric mild hyperphenylalaninemia.

Unlike maternal phenylketonuria (PKU) which produces severe birth defects when untreated during pregnancy, maternal non-PKU mild hyperphenylalaninemia (MHP) has a less severe impact but whether it is benign or may have long-term consequences for offspring has been unclear. From an international survey of maternal MHP we obtained information about 86 mothers (blood phenylalanine (Phe) 150-720 mumol/l), their 219 untreated pregnancies and 173 offspring. Spontaneous fetal loss and congenital anomalies were no more frequent than normally expected. Median Z-scores for birth length and birth head circumference and offspring IQ (100), however, were significantly lower for maternal Phe > 400 mumol/l than for maternal Phe < 400 mumol/l, in which the median offspring IQ was 108. Data on maternal MHP from the prospective Maternal PKU Collaborative Study (MPKUCS) are as yet incomplete but seem to be conforming to the general pattern of the international survey. We conclude that maternal blood Phe levels above 400 mumol/l in maternal MHP are associated with lower birth measurements and slightly lower offspring IQ. It would seem that dietary intervention to lower the maternal Phe levels to below 400 mumol/l might be indicated in maternal MHP pregnancies with the higher blood Phe levels.

Adult↗
PubMed1996

Maternal phenylketonuria: magnetic resonance imaging of the brain in offspring.

Phenylketonuria (PKU) produces white matter changes identifiable by magnetic resonance imaging. These changes occur postnatally. Offspring of untreated mothers with PKU also have a brain effect, expressed as microcephaly and mental retardation. This effect occurs prenatally. To determine whether the white matter changes seen in PKU are also present in maternal PKU offspring, despite the different developmental stages of exposure to PKU, we performed brain magnetic resonance imaging studies in seven maternal PKU offspring, five from essentially untreated pregnancies and two from treated pregnancies. None had white matter changes, although the one offspring with PKU had delayed myelination. However, hypoplasia of the corpus callosum was present in three of the four offspring from untreated pregnancies and in the offspring from a maternal PKU pregnancy not treated until the third trimester. Unlike PKU, white matter changes are not a feature of the brain effect in maternal PKU. However, hypoplasia of the corpus callosum is a feature of maternal PKU and is probably a result of inhibition of corpus callosum development at 8 to 20 weeks of gestation. The hypoplastic corpus callosum could be a marker for brain effect in maternal PKU and may have implications for the cognitive deficits in these offspring.

Adolescent↗
PubMed1994

Maternal mild hyperphenylalaninaemia: an international survey of offspring outcome.

Maternal phenylketonuria (PKU) has adverse effects on the offspring including microcephaly, mental retardation, congenital heart disease, and intrauterine growth retardation. Maternal non-PKU mild hyperphenylalaninaemia (MHP) is believed to be benign, but whether there may be long-term consequences to offspring is unclear. In an international survey we have obtained information about 86 mothers with MHP (blood phenylalanine 167-715 mumol/L), their 219 untreated pregnancies, and 173 offspring. Spontaneous fetal loss (13% of pregnancies), congenital heart disease (2.3% of offspring), and severe non-cardiac anomalies (2.9% of offspring) occurred at frequencies within expected limits for the general population. For weight and length at birth the median percentile was the 50th but that for birth head circumference was the 25th. Median z-scores for birth length and head circumference were significantly lower for offspring of mothers with phenylalanine concentrations above 400 mumol/L than for those whose mothers had lower values (p = 0.05 and p = 0.005, respectively). The median intelligence quotient (IQ) of the offspring (3-27 years) was 100 for those whose mothers had higher phenylalanine concentrations and 108 for those of the lower phenylalaninaemia group. However, offspring IQ correlated slightly more closely with maternal IQ (r = 0.53, p < 0.001) than with maternal phenylalanine concentration (r = 0.45, p = 0.02). Maternal MHP does not seem to have serious consequences for the fetus. A maternal phenylalanine concentration of less than 400 mumol/L does not warrant intervention. Nevertheless, maternal blood phenylalanine above this value is associated with slightly lower birth measurements and offspring IQ than lower maternal blood phenylalanine concentrations.

Adolescent↗
PubMed1993

The use of gelatin capsules for ingestion of formula in dietary treatment of maternal phenylketonuria.

Maternal phenylketonuria (PKU) represents a high risk for birth defects, including mental retardation, in offspring. Thus, it could cancel gains represented by the prevention of PKU-induced mental retardation in the current generation. Effective dietary treatment of maternal PKU pregnancies could avoid this potentially tragic occurrence. However, dietary compliance is often difficult because a necessary component of the diet, medical nutritional formulas, often have an unpleasant taste and odour. We treated the second pregnancy of a phenylketonuric women who had required extended hospitalization during her first pregnancy because of poor formula tolerance, and who had similar difficulty in the second pregnancy. To alleviate this problem, we developed a system whereby she could pack the formula into gelatin capsules for ingestion. Packing and ingestion of 20 capsules required less than 30 minutes three times a day. With capsules her blood phenylalanine level was almost always within the recommended range of 120-360 mumol/L (2-6 mg/dl) and hospitalization was not required. The phenylalanine content of the capsules was easily accommodated by a small reduction in allowable food. Other amino acid levels, including tyrosine and other essential nutrient levels, were normal. We believe that using gelatin capsules for formula ingestion can be very beneficial in the management of maternal PKU pregnancies and could be extended to the dietary treatment of other inborn errors of metabolism.

Adult↗
PubMed1992

Comparison of phenylketonuric and nonphenylketonuric sibs from untreated pregnancies in a mother with phenylketonuria.

Two children, one with phenylketonuria (PKU) and the other nonphenylketonuric, from untreated pregnancies in a mother with PKU provided the opportunity to compare the degree of damage from maternal PKU between these genotypically different fetuses. Both the phenylketonuric offspring and her nonphenylketonuric sib were microcephalic at birth and had congenital anomalies, esophageal atresia in the former and congenital dislocation of the hip in the latter. However, the phenylketonuric child also had intrauterine growth retardation while the nonphenylketonuric sib had normal weight and length at birth. Both children are mentally retarded with an IQ below 50 in the phenylketonuric child despite early dietary treatment for PKU and an IQ of 54 in the nonphenylketonuric sib. Both children also have hypoplasia of the corpus callosum and enlarged cerebral ventricles. This experience and review of the literature indicates that the residual liver phenylalanine hydroxylase activity of a nonphenylketonuric fetus offers little or no protection from damage in untreated maternal PKU. Consequently, the outcome in maternal PKU is likely to depend on control of the maternal biochemical abnormalities in the mother regardless of whether the fetus has or does not have PKU.

Abnormalities, Multiple↗