Treatment outcome of maternal phenylketonuria.
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Adult↗
Biomedical subjects
C Azen
Publications and source records attributed to C Azen.
Blood phenylalanine levels and intelligence of 10-year-old children with PKU in the National Collaborative Study.
Dietary intakes and blood phenylalanine levels of 125 10-year-old children with PKU are reported. Of those patients, 59 discontinued the special diet at 6 years, 16 discontinued at 8 years, 5 discontinued at 6 years but returned to the diet at 8 1/2 years, and 45 continued the diet to 10 years. Phenylalanine intake was determined by 2-day diet records. Blood phenylalanine concentrations revealed a lack of clear distinction between the diet groups; therefore, regression analysis was performed on the group as a whole. The analyses revealed significant relationships between blood phenylalanine levels from ages 6 to 10 years and each of the cognitive outcome variables, after the influences of parental IQ and the age at which treatment was initiated were controlled for. Intelligence test scores were also related to phenylalanine levels between ages 3 1/2 and 5 1/2 years. The findings suggest that dietary restriction of phenylalanine should continue in patients with PKU through at least 10 years of age.
Child↗
Effect of age at loss of dietary control on intellectual performance and behavior of children with phenylketonuria.
We determined the effect on intellectual performance and behavior of the age at which dietary control was lost in 119 10-year-old children with phenylketonuria (PKU) who had started on a diet low in phenylalanine before the age of 65 days. The children's diets were considered to be out of control when their blood phenylalanine concentration persistently exceeded 15 mg per deciliter. The age at which control was lost was the best, and frequently the only, predictor of the child's IQ at the age of 8 or 10 years and of the deficit in the child's IQ as compared with those of his or her unaffected siblings or parents. The age at which control was lost was also the best predictor of the deficit in scores on the Wide Range Achievement Test of children with PKU at the age of eight, as compared with their unaffected siblings, and of behavior problems (Louisville Behavior Checklist). Variables that were not significant included the maximal phenylalanine concentration before dietary therapy, the age at which treatment was started, and the family's coping abilities. The greatest deficiencies in all of these outcomes were observed among children who were out of dietary control before the age of six years. The highest correlation between the IQs of the children with PKU and their respective parents was observed among the children still on the diet at the age of eight years; the lowest, among those who had poor dietary control before the age of six. These findings suggest that phenylalanine restriction should continue after the age of eight years in children with PKU.
Adolescent↗
Paired comparisons between early treated PKU children and their matched sibling controls on intelligence and school achievement test results at eight years of age.
Early-treated PKU children were compared to their matched non-PKU sibling controls on Wechsler Intelligence Scale for Children (WISC) and Wide Range Achievement Test (WRAT) results at age 8. Fifty-five PKU children had mean WISC Full Scale IQ score of 100, in comparison to a mean of 107 for their matched sibling controls (p = 0.001). Treatment parameters significantly correlated with sibling-PKU IQ score differences included maximum diagnostic phe level (r = 0.244, p = 0.036) and phe levels at age 6 (r = 0.329, p = 0.007) and at age 8 (r = 0.489, p less than 0.0005). Fifty PKU subjects scored significantly lower than their matched sibling controls on standard scores of the WRAT Reading (102 vs. 107, p = 0.016) and Arithmetic (96 vs, 101, p = 0.006) subtests, and lower, but not significantly so, in Spelling (100 vs. 103, p = 0.145). When the sample was grouped according to diet status at age 8, on-diet PKUs scored at or above the level achieved by their siblings on all three scales of the WISC and all three WRAT subtests, whereas the off-diet group scored from 7 to 13 points below their siblings on all measures. These results suggest that PKU children should restrict phe intake at least through their school years.
Child↗
Correlates of intelligence test results in treated phenylketonuric children.
The Collaborative Study of Children Treated for Phenylketonuria was initiated in 1967. The data presented are based on findings in 132 children treated from near birth to 6 years of age. Two treatment groups were randomly formed. The target for blood phenylalanine was 1.0 to 5.4 mg/100 ml for group 1 and 5.5 to 9.9 mg/100 ml for group 2. Although mean blood phenylalanine levels for both groups initially fell within the prescribed ranges, a steady increase over time resulted in mean six year levels of 11.4 mg/100 ml and 13.0 mg/100 ml for the two groups, respectively. Because it was not possible to maintain the prescribed differences in blood phenylalanine levels between the two groups, they were combined for further analyses. The mean IQ of the total sample at age 6 years was 98 on the Stanford-Binet Intelligence Scale. Multiple regression analysis showed that, among selected treatment and psychosocial factors, the most important predictors of IQ for 6-year-old children were: (1) mothers' intellectual ability (as measured on the Wechsler Adult Intelligence Scale); (2) age at which the subjects were first treated; and (3) how well the subjects adhered to the phenylalanine-restricted diet. It was concluded that optimal early treatment will result in normal levels of intelligence at 6 years of age.
Age Factors↗
The diagnosis of phenylketonuria: a report from the Collaborative Study of Children Treated for Phenylketonuria.
One hundred ninety-five infants who met diagnostic criteria for enrollment in the Collaborative Study of Children Treated for Phenylketonuria (PKU) underwent a standard three-day challenge with 180 mg/kg/day of phenylalanine for confirmation of diagnosis. A sustained rise in serum phenylalanine levels of greater than 20 mg/dl was observed in 166 infants (85.1%), compatible with the diagnosis of classical PKU. In the remaining 29 infants (14.9%), the serum phenylalanine concentration either did not reach 20 mg/dL or, having achieved this level, subsequently declined below this point by 72 hours. It was agreed that these 29 patients had variant PKU and they were dropped from the Collaborative Study. We recommend that all infants diagnosed as having classic PKU undergo a challenge to confirm the diagnosis and need for continued treatment.
Humans↗
Intellectual assessment of 111 four-year-old children with phenylketonuria.
Of the 216 children with phenylketonuria (PKU) who were initially enrolled in the Collaborative Study of Children Treated for Phenylketonuria, 203 were placed on dietary therapy between 3 and 92 days of age. Of these, 111 are now at least 4 years of age and constituted the sample for the present analysis. Their mean IQ on the Stanford Binet Intelligence Scale was 93 (1972 norms). The children assigned to two treatment groups based on "moderate" and "low" serum phenylalanine levels were comparable on their IQs at age 4, although many of the children could not be maintained in the specified categories. Females scored a significantly higher mean IQ than males (97 vs 90). Those children for whom dietary treatment was initiated during the first month of life scored a mean IQ of 95, compared with 85 for those initially treated from 31 to 65 days. However, the interpretation of dietary inception data may have been contaminated by familial and psychosocial factors. The PKU Collaborative Study is still in progress in 15 clinics located in 11 states.
Child, Preschool↗
A computerized procedure for estimating nutrient intake.
A procedure was devised for computing intake in terms of calories, total protein, phenylalanine, carbohydrate, and fat. The procedure used a magnetic tape containing 3,122 numbered food items. The nutrient composition of each food was reported for 100 g of the edible portion of the food. In addition, diet diaries were prepared in which the foods eaten during the preceding 24-hr period, the code for each food corresponding to the number for the same item on the magnetic tape, and the number of units of each food eaten were recorded. A computer program then was written that calculated the amounts of intake per day for each nutrient. Application of the procedure for 42 consecutive days on the daily diet records of 43 adult carriers of the phenylalanine hydroxylase enzyme formed the data base used to determine if aspartame significantly increased levels of phenylalanine in the blood. Adaptations of the procedure permit calculations of intake for periods from 1 to 30 days and analyses of additional nutrients including calcium, phosphorous, iron, vitamin A, thiamine, riboflavin, niacin, and ascorbic acid.
Computers↗
Maternal phenylketonuria: an international study.
Maternal phenylketonuria (PKU) syndrome results in multiple congenital anomalies in the offspring, usually consisting of microcephaly, intrauterine growth retardation, dysmorphology, and congenital heart disease. Pregnancies treated preconceptionally with a phenylalanine-restricted diet and control of maternal blood phenylalanine levels within the recommended range result in normal offspring. However, in this 15-year study, several significant factors resulted in microcephaly in 27% of the offspring, and 7% exhibited serious congenital heart disease. These results occurred chiefly in women with mean IQ scores of 83 associated with low socioeconomic status and decreased educational achievement. Another important factor associated with suboptimal control of blood phenylalanine levels during pregnancy was the fact that most pregnancies were not carefully planned and occurred in women off dietary treatment with phenylalanine-restricted products. These results indicate that greater effort must be developed to assist women with PKU in remaining on diet during their reproductive years. It appears that continued adherence to the diet, resulting in normal maternal intelligence, is an important contribution to improved fetal development.
Female↗