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Dietary Management and Health Consequences

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Historical perspective of Phe-restricted diet

Success of the Phe-Restricted Diet: The US Collaborative Study (1967-1999)

Age     Finding
4 IQ similar to general population61
6 IQ related to age of starting diet32
8 Subjects on-diet performed better on IQ and school achievement tests than subject off-diet32
Adult Adults on-diet had fewer medical and mental disorders and higher cognitive test scores than subjects off-diet63
* Result is a philosophy of "Treatment for Life" at most clinics in the United States63
  • Longitudinal study initiated in 1967 to assess effects of Phe-restricted diets on physical, cognitive and psychosocial development in children61
  • Study groups comprised of:
    • 216 4-year olds with PKU
    • 228 controls (9 siblings with untreated PKU, 219 nonaffected siblings)
  • 17 years of results revealed:
    • At 4 years of age, IQ (mean 93) was within range of the general population62
    • At 6 years of age, IQ was found to be significantly related to the age that treatment was initiated, emphasizing the value of starting early32
    • At 8 years of age, subjects remaining on-diet performed better on IQ and school achievement tests than subjects who resumed a normal diet after age 632
    • 15-year follow-up revealed a lower frequency of medical and mental disorders and higher cognitive test scores among subjects continuing diet63

These findings have led to the “Diet for life” philosophy used in most clinics across the U.S. and world.

Numerous health consequences have been associated with a Phe-restricted diet, including neurocognitive deficits,4 weight gain/obesity, growth retardation,24,64,65 nutritional problems,2,66-68 and bone mass reduction.20

Health consequences of the Phe-Restricted Diet

Numerous health consequences associated with Phe-restricted diet

Numerous health consequences have been associated with a Phe-restricted diet including neurocognitive deficits,4 weight gain/obesity and growth retardation,24,64,65 nutritional problems,2,66-68 and bone mass reduction.20

Suboptimal outcomes in cognitive functioning

Patients who follow the Phe-restricted diet are not immune to the neurocognitive effects of PKU.4 Even those who manage the disease with dietary management strategies may have changes in IQ, processing speed, attention, memory, inhibition, and motor control.4

Higher weight /obesity in patients with PKU

The growth patterns, height and weight of 133 children with PKU (ages 2-10) who were participating in the Collaborative Study of Children Treated for Phenylketonuria were compared with data from the National Center for Health Statistics (NCHS) for unaffected children. Higher Phe levels in the PKU group were associated with higher weight levels, more so for girls than for boys.64 There were statistically significant mean weight (kilogram) value differences when comparing females from the PKU vs. the NCHS group at 4 years of age (17.32 kg vs. 15.88 kg) and at 7 years of age (25.20 kg vs. 22.24 kg). For males 5 years of age, mean weight value differences (kg) were also statistically significant (19.97 kg vs. 18.55 kg).64

A 1-year longitudinal study assessed nutrient intake, physical growth, and plasma amino acid concentrations in 58 children with PKU (2-12 years of age) who were undergoing therapy with medical food. While linear growth of children with PKU was within the normal limits, obesity was present in a significant number of these children.65

Based on these studies, energy intake, physical activity, and weight of patients with PKU should be carefully monitored.24

Impact of nutritional deficiencies

Patients who use dietary management strategies have marked nutritional deficiencies or issues that may cause serious sequelae:

  • Adolescents and adults with PKU who have stopped or relaxed their Phe-restricted diet are at risk for vitamin B12 deficiency, which can cause a wide range of clinical effects including anemia, neuropathy, and psychiatric disorders66
  • Synthetic protein is not always optimally metabolized, leading to inadequate growth of patients with PKU67
  • Significant correlation between natural protein (not synthetic protein) and head circumference growth in the first 3 years of life68
  • Formulas often do not provide adequate trace minerals and other nutrients2

An improvement of protein quality may be the key to normal growth and body composition in PKU children67

Bone mass reduction

Nutritional deficiencies are associated with declines in bone mass, leading to osteopenia and osteoporosis. In a clinical study of PKU patients, mean age 25 years, on a Phe-restricted diet, 39% developed osteopenia, and 7%, osteoporosis.20