Description of Pilot
Blood Phe Levels
Final Report and Recommendation to the Legislature
PKU Low Protein Medical Food Pilot
Texas Department of Health - Newborn Screening
Case Management Program
Rider 58, General Appropriations Act
76th Legislature, 1999
Rider 58 from the 76th Legislature, General Appropriations Act 2000-2001 Biennium, directed the Texas Department of Health (TDH) to conduct a two-year study of the effect of low protein food on the management of children with phenylketonuria (PKU). TDH allocated $150,000 in Fiscal Year 2000 and $150,000 in Fiscal Year 2001 to conduct a pilot project to assess the cost effectiveness of providing prescribed medical foods to children ages 0 to 5 with PKU. This budget was expanded January 2001 to ensure adequate numbers of participants in the pilot as recommended in the interim report to the 77th Legislature.
PKU is a rare, inherited metabolic disorder that causes mental retardation if untreated. Approximately one of every 35,200 infants in Texas is born with PKU, which is the result of a deficiency of a liver enzyme. This enzyme deficiency leads to elevated levels of the amino acid phenylalanine (blood Phe) in the bloodstream.
At the present time, a strict diet low in Phe is the only treatment for PKU. If the diet is started early enough and closely followed, the child's development will be normal in almost all cases. The diet must be carefully planned to allow enough Phe for the child to grow normally, yet not enough to produce the harmful effects of excessive Phe. A child's needs depend on the severity of the enzyme deficiency and the child's age, growth rate, and current state of health. The right amount of Phe for the child is determined through blood tests that measure the amount of Phe in the child's blood. The child’s diet prescription is adjusted by a physician and nutritionist depending on the blood Phe level.
The PKU Low Protein Medical Food Pilot Project was designed to increase the consumption of low protein medical foods, therefore facilitating access to proper diet management. Medical food order forms were completed under the guidance of the participants’ metabolic nutritionist. The medical foods were then shipped directly to the participants’ families.
TDH determined the effectiveness of the PKU Low Protein Medical Food Pilot Project according to the following three goals:
- Blood Phe levels will be within the established treatment range for control of PKU.
- Growth will be maintained.
- IQ will be maintained.
Description of Pilot
A total of 64 children aged 0-11 participated in this two-year pilot project. Participants were recruited from five medical facilities providing care for metabolic disorders:
- University of Texas Health Science Center (UTHSC) in San Antonio (n=16)
- University of Texas Southwestern Medical Center (UTSW) in Dallas (n=25)
- Genetics Institute of Austin (n=3)
- University of Texas Health Science Center in Houston (n=7)
- Texas Children’s Hospital/Baylor College of Medicine in Houston (n=13)
Baseline information, described below, was collected at the initial enrollment. Subsequently, clinic staff saw participants quarterly and additional information was gathered on:
- Medical food orders:
- Types of medical foods that were ordered
- Parent-reported assessments of the frequency of consumption of each type of medical food (e.g., weekly, daily)
- Comments on the medical foods and their delivery
- Blood Phe levels
- Physical measurements (height, weight, and head circumference)
Psychological tests were conducted at the beginning and end of each child’s participation to measure general mental development.
The PKU Low Protein Medical Food Pilot experienced two types of limitations: program interruption and incomplete or missing data. From December 30, 2001, to March 14, 2002, there was an interruption in the delivery of medical foods because the contractor withdrew its services and a new contractor had to be found to complete the pilot. This interruption resulted in:
- A disruption in food delivery to participants
- A change in the kinds of food that could be ordered after the resumption of medical food delivery
Incomplete or missing data included:
- Irregular timing of the physical growth measurements (e.g., not all measurements were recorded on a quarterly basis)
- Improbable physical growth measurements
- Only two-thirds of the participants participated in a second psychological testing session (post-test)
- There were differing sample sizes for every variable used in the analyses
Blood Phe levels, growth, and mental development were compared at baseline and during the pilot project. The date on which a parent/guardian signed the pilot project consent form was considered as the baseline or pilot start date. Measures recorded on subsequent dates were considered as occurring during the pilot. The impact of the interruption of food deliveries on blood Phe levels and physical growth was also assessed.
Comparisons were also made among sites. No significant differences were found.
Blood Phe Levels
Blood Phe levels for children with PKU are in control when they are in range of 2.0 to 6.0 mg/dl (milligrams per deciliter). For children with PKU, levels below and above that ideal range are associated with harmful physical and mental effects.
Results indicated that mean blood Phe levels rose throughout the pilot.
- The mean blood Phe level during the pilot (6.9 mg/dl) was above the ideal range and higher than the baseline (6.2 mg/dl). This finding indicates that blood Phe levels rose throughout the pilot and remained higher than the ideal range.
- There was no significant difference in the percentages of children who were below, within, and above the ideal range.
Further analyses determined that the interruption in medical food delivery affected blood Phe levels:
- The mean blood Phe level after resumption of medical food delivery (7.6 mg/dl) was higher than the mean blood Phe levels recorded before the interruption in medical food delivery (6.6 mg/dl) (Figure 1)
- There was a gradual increase in mean blood Phe levels that occurred at the same time as the interruption in medical food delivery
- The percentage of children whose measurements were below the ideal range decreased after resumption of medical food delivery
- These findings indicate that the availability of medical foods did not contribute to a significant decrease in blood Phe levels.
The association between medical food delivery and blood Phe levels was significant, although it was not strong. This may indicate that there are other factors (e.g., compliance with diet) that are associated with the increase in blood Phe levels.
Note: Error bars represent 95% confidence intervals for the mean blood Phe levels during the periods of baseline, before the interruption, during the interruption, and resumption of medical food delivery.
Growth measurements of height, weight, and head circumference were measured and scaled to percentile ranks according to the 2000 Center for Disease Control (CDC) growth charts for age and gender. A comparison of baseline measures and measures taken during the pilot indicates:
- There was no significant difference between the percentile ranks of the participants’ height, weight, and head circumference at baseline and during the pilot. These results indicated that participants’ growth was maintained throughout the study at similar rates to normal growth.
- Thus the low protein food did not have a deleterious effect on physical growth.
- The interruption in medical food delivery does not appear to be associated with effects on physical growth.
- There were no significant differences among the percentile ranks of the participants’ measurements. These results indicate that all growth occurred at rates similar to normal growth.
Licensed psychologists performed two psychological evaluations at the beginning and end of each child’s participation. Each evaluation consisted of the Vineland Aptitude Test and either the Bayley Scales of Infant Development or the Differential Abilities Scale, depending on age.
Results of the evaluations were reported in standard IQ score format for which the average or normal range for both mental and motor abilities ranges from 85 to 115. Significant changes are typically defined as changes of one standard deviation (15 points) or more on one or more parts of the tests (subtests). Figure 2 displays the significant changes in one or more psychological subtest scores for the 40 subjects with both pre-test and post-test data (i.e., stable scores, a significant increase on one or more subtests, a significant decrease on one or more subtests, both an increase and a decrease on two or more subtests).
As expected, participants with a decrease on one or more subtest scores had a higher mean blood Phe level throughout the study than other participants.
Results of the PKU Low Protein Medical Food Pilot indicated the following:
- The interruption in medical food delivery was a critical and unexpected occurrence during the pilot. This interruption appears to have had an impact on the range of phenylalanine levels during this period.
- Mean blood Phe levels rose throughout the pilot and remained higher than the established treatment range for control of PKU.
- Participants’ physical growth was maintained throughout the study at similar rates to normal growth.
- Participants with a decrease on one or more psychological subtest scores had a higher mean blood Phe level throughout the study.
- When the family uses the low protein food appropriately to maintain Phe levels in the ideal range the low protein food is effective in the management of a child with PKU.
If medical advice is followed, the provision of medically indicated medical foods is effective in the management of children with PKU.
Therefore, the department recommends that consideration be given to mandating insurance coverage in Texas for medically indicated medical foods for people with PKU.