Low Phenylalanine Diet for Mothers With Phenylketonuria (PKU)

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details. Identifier: NCT00065299
Recruitment Status : Completed
First Posted : July 22, 2003
Last Update Posted : June 24, 2005
Information provided by:
Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD)

July 21, 2003
July 22, 2003
June 24, 2005
May 1984
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Low Phenylalanine Diet for Mothers With Phenylketonuria (PKU)
Effects of Maternal Phenylketonuria (PKU) on Pregnancy Outcome
Phenylketonuria (PKU) is a rare genetic condition. If not treated, PKU can cause severe mental retardation. Women with PKU are advised to eat a special diet when pregnant to prevent mental retardation in their children. This study will evaluate the effects of that diet on the children of mothers with PKU.

PKU is an autosomal recessive trait caused by the absence of phenylalanine hydroxylase. Phenylalanine hydroxylase is an enzyme involved in the metabolism of phenylalanine (Phe). When phenylalanine hydroxylase is absent or defective, Phe levels rise and toxic Phe metabolites accumulate, causing central nervous system injury. PKU is a treatable disease. Affected individuals must adhere to a diet low in Phe during childhood. Women with PKU should also adhere to a low Phe diet before and during pregnancy to avoid fetal damage. The offspring of women with untreated maternal hyperphenylalaninemia (HPA) usually exhibit mental retardation, microcephaly, growth retardation, and other congenital anomalies. This study will examine the effect of a restricted Phe diet on reproductive outcome in women with maternal HPA.

Participants in this study will be women with HPA whose blood Phe values are persistently greater than 4 mg/dl. Those women with blood Phe values consistently greater than 8 mg/dl will be placed on a Phe restricted diet to maintain plasma Phe concentrations between 2 and 8 mg/dl. This level of control is practical and achievable. Due to a gradient of increasing Phe level from mother to fetus, levels in the latter would vary from 3.5 to 12 mg/dl; these levels are usually associated with normal outcomes. Women will be monitored throughout their pregnancy on obstetric, biochemical, and nutritional parameters. Women on the Phe restricted diet will be given enough Phe-limited protein, calories, vitamins, and minerals to maintain adequate nutritional status. Folate supplementation will be provided. If indicated clinically, tyrosine (Tyr) and supplemental trace metals will be prescribed.

A matching control sample of women and their offspring will be developed in collaboration with associated coordinating and collaborating centers. The offspring of both groups of mothers will be followed as long as the project permits. Those offspring born to mothers admitted to the project during the first 2 to 3 years of the study will be assessed on their intellectual ability and physical health, as well as academic achievement in school. Those admitted during the last 3 to 4 years of the study will be assessed on their intellectual ability and physical health, recognizing that limited data will be available for these offspring.

Not Applicable
Allocation: Non-Randomized
Masking: None (Open Label)
Primary Purpose: Treatment
Behavioral: Restricted phenylalanine diet
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*   Includes publications given by the data provider as well as publications identified by Identifier (NCT Number) in Medline.
Same as current
April 2000
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Inclusion Criteria

  • Live in community setting
  • Become pregnant or give birth during the term of the investigation
  • Identified early in pregnancy
  • Dietary therapy instituted prior to conception whenever possible
  • Diagnosis of PKU based on results of Phe challenge, or clear diagnostic evidence in medical record
  • Blood Phe > 4 mg/dl
  • Intellectually able to understand and comply with the requirements of the Phe restricted diet, understand an informed consent, and adequately communicate with clinic personnel
  • IQ > 70

Inclusion Criteria for Controls

  • Heterozygous sisters to HPA women
  • Matched control from maternity facility; pregnancy and offspring from a non-PKU female and a PKU male

Exclusion Criteria

  • Women with evidence of pterin defect
Sexes Eligible for Study: Female
Child, Adult, Older Adult
Contact information is only displayed when the study is recruiting subjects
United States
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Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD)
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Principal Investigator: Richard Koch, M.D. University of Southern California
Principal Investigator: Reuben Matalon, M.D. University of Illinois at Chicago
Principal Investigator: Bobbye M. Rouse, M.D. University of Texas at Galveston
Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD)
May 2000

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP