Malcolm L. Williamson

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<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.

Preliminary report on the effects of diet discontinuation in PKU

A collaborative study of diet discontinuation in children with PKU was initiated in 1973. Children treated with the phenylalanine-restricted diet since early infancy were randomly assigned to continue or discontinue dietary therapy at age 6 years after parental consent was obtained. The 115 children participating in this study range in age from 8 to 13 years. At 6 years of age, the IQ of continuers and discontinuers was 101 and 97, respectively. At 8 years, WISC Full-Scale IQ scores adjusted for mean differences on the 6-year Stanford-Binet IQ were 101 for continuers and 98 for discontinuers (P = 0.075). School performance measured by the Wide Range Achievement Test showed significant differences on reading (3.9 vs 3.2) and spelling (3.3 vs 2.9) grade placement, although scores were above actual grade placement (2.7 vs 2.6) for both groups. Continuers and discontinuers were not different in arithmetic scores, with performance at grade placement of 2.7 and 2.6 respectively. Although these data are preliminary in nature, they suggest that subtle changes in cerebral function may occur in children with PKU in whom the phenylalanine diet has been discontinued.

Cardiovascular effects of increased intra-abdominal pressure in newborn piglets☆

Abstract An experimental model for measuring the cardiovascular effects of increased intra-abdominal pressure was devised and described. Aortic and pulmonary artery pressures were found not to vary with increasing intra-abdominal pressure. The pH, pCO 2 , and pO 2 were measured from the aorta, pulmonary artery, and inferior vena cava. No statistical difference in these parameters could be found with increasing intra-abdominal pressure. Cardiac output and cardic index decreased sharply with increasing intra-abdominal pressure. These data emphasize the importance of intra-abdominal pressure on cardiovascular function in newborn animals.

Cognitive development and dietary therapy in phenylketonuric children.

Abstract Phenylketonuric children (now four years of age or older) were given intelligence and language tests to ascertain their present levels of cognitive functioning. These intellectual abilities were then evaluated in relation to the childrens ages at the time diets low in phenylalanine were begun. The influence of distorting nontreatment factors, such as family level of intelligence and sociologic variation, was ascertained by computation of a multiple-regression equation analysis. Examination of the data revealed a consistent inverse relation between present intellectual ability and age of dietary inception. The children treated within one month after birth scored an average of 33 IQ points higher than those for whom treatment was initiated within their fourth and sixth years of life.

Use of aspartame in phenylketonuric heterozygous adults

Asparatame, a new artificial sweetener, was administered to 45 obligate phenylketonuric adults for 28 wk. This new sweetening agent was well tolerated, and no untoward medical or biochemical changes were noted.

Preliminary report of the effects of diet discontinuation in phenylketonuria

The accepted therapy for phenylketonuria (PKU) (McKusick 26160) is the use of a diet restricted in phenylalanine (phe). In the United States, dietary therapy has usually been terminated between four and six years of age; however, some clinicians prefer to delay diet discontinuation until adolescence or later. Murphy (1969) initially suggested that termination of dietary therapy during childhood might be harmful. Dietary termination in two children was followed by adverse changes in behaviour and reduced intellectual performance. Subsequently, Cabalska et al. (1977) and Smith et al. (1978) recorded similar findings. The Collaborative Study of Children Treated for Phenylketonuria (Williamson et al., 1977; Koch et al., 1973) has begun to evaluate the effects of discontinuing dietary therapy at age six years (Williamson et al., 1979). This report presents findings on academic ability of children off diet from age six to eight years in comparison to a group maintained on treatment.

A cooperative study of two methods for phenylalanine determination: McCaman-Robins fluorimetric and microbiologic inhibition methods

Either the McCaman-Robins fluorimetric method or the microbiologic inhibitionassay can be used effectively to identify phenylketonuric individuals. Physicians who routinely use either of these methods to screen and follow up all newborn infants can be quite confident that infants with phenylketonuria will be detected.

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.

High-calorie parenteral alimentation: Serum lactic and pyruvic acid levels in immature dogs during infusion with concentrated glucose solutions

Abstract Solutions of glucose of varying concentrations (10%–25%) were administered through central venous catheters to immature dogs in volumes greater than those employed in clinical total parenteral infusion therapy. Blood lactate and pyruvate levels were not raised during the course of the infusion, irrespective of the glucose concentration employed. Acidosis was not produced by these infusions. Glucose concentrations of approximately 20% were utilized most effectively, as demonstrated by total glucose retention. Clinical lactic acidemia is probably not adversely affected by continued infusion of high concentrations of glucose.