Finding the fertile woman with phenylketonuria

Eur J Obstet Gynecol Reprod Biol. 2008 Apr;137(2):131-5. doi: 10.1016/j.ejogrb.2007.12.011. Epub 2008 Feb 8.


This review highlights two groups of women with phenylketonuria (PKU) who are at risk of producing offspring with maternal phenylketonuria (MPKU) embryopathy: (I) those not yet diagnosed; (II) those lost to follow-up. The world literature is reviewed, including that published from the International MPKU Collaborative Study (MPKUCS) and evidence is presented to support our hypothesis that at least 10% of subjects with untreated "classical PKU" will have relatively normal intellectual function and that a significantly higher percentage of the less severe "variants" (who make up approximately 50% of the total) will have IQ's measured within the normal range. The offspring of the females with these PKU variants, however, are not as fortunate-most suffering profound damage in-utero if the pregnant woman is not treated. However, the offspring of the mildest variant (untreated) "non-PKU mild hyperphenylalaninemia (MHP)" - blood phenylalanine 200-600 micromol/L - appear to be unaffected. This latter variant makes up 10-15% of the total. Many of these women, born before neonatal screening began in the jurisdiction of their birth, are unaware of their disease. Others, whose diet was discontinued in childhood, may not remember why they were on special diets. Our literature review has revealed reports, since 1990, of 60 women with previously undiagnosed PKU, most with relatively normal intellectual function, who produced 119 offspring, virtually all profoundly damaged. It is pointed out that the recent trend, in industrialized countries, of delayed child-bearing may be a factor. Reports are presented from various jurisdictions showing that up to 10% of known women with PKU in the reproductive age group have been lost to follow-up. "Selective Prenatal Screening or Case-Finding" for fertile women with PKU is recommended and a template is presented.

Publication types

  • Research Support, N.I.H., Extramural
  • Review

MeSH terms

  • Female
  • Fertility / physiology*
  • Genetic Testing*
  • Humans
  • Mutation / genetics
  • Phenylalanine Hydroxylase / genetics
  • Phenylketonuria, Maternal / diagnosis*
  • Phenylketonuria, Maternal / genetics
  • Phenylketonuria, Maternal / physiopathology
  • Pregnancy


  • Phenylalanine Hydroxylase