Journal of Inherited Metabolic Disease

, Volume 37, Issue 1, pp 39–42 | Cite as

Maternal Phenylketonuria International Collaborative Study revisited: evaluation of maternal nutritional risk factors besides phenylalanine for fetal congenital heart defects

  • Shoji Yano
  • Kathryn Moseley
  • Teodoro Bottiglieri
  • Erland Arning
  • Colleen Azen
Original Article


Maternal phenylketonuria (MPKU) is known to affect fetal outcome, often being associated with microcephaly and congenital heart defects (CHD) if the maternal diet is not appropriately managed. We hypothesized that other nutrients aside from phenylalanine (Phe) may have significant effects on fetal outcome in MPKU pregnancies. The 416 pregnancies that resulted in live births reported in the Maternal PKU Collaborative Study (MPKUCS) were grouped according to whether or not the offspring were diagnosed with CHD. The groups were compared on first-trimester values of maternal data, including weight gain, plasma amino acids, protein and Phe intake, and red blood cell (RBC) folate. Patients were also grouped by first-trimester average blood Phe (≤910 μmol/L and >910 μmol/L) and then divided by total natural protein and medical food intake. The CHD group of 28 offspring had significantly higher blood Phe and lower proline, valine, methionine, isoleucine, leucine, lysine, arginine, and RBC folate. A significantly higher risk for CHD was found in the groups with lower natural protein and medical food intake, regardless of blood Phe levels. Insufficient natural protein and medical food product intake appears to be a risk factor for CHD independent of first-trimester plasma Phe levels. Low RBC folate and plasma methionine levels in the CHD group may suggest involvement of global DNA hypomethylation.


Congenital Heart Defect Plasma Amino Acid Congenital Heart Defect Large Neutral Amino Acid Plasma Methionine 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.



Analysis for this project was supported in part by NIH NCRR SC-CTSI Grant Number UL1 RR031986. We thank our mentor, Dr. Richard Koch, for his work on the MPKUCS. We also appreciate Ms. Carolina Coleman for her dedication to and compassion for this project.

Conflict of interest



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Copyright information

© SSIEM and Springer Science+Business Media Dordrecht 2013

Authors and Affiliations

  • Shoji Yano
    • 1
  • Kathryn Moseley
    • 1
  • Teodoro Bottiglieri
    • 2
  • Erland Arning
    • 2
  • Colleen Azen
    • 3
  1. 1.Genetics Division, Department of Pediatrics, LAC + USC Medical Center, Keck School of MedicineUniversity of Southern CaliforniaLos AngelesUSA
  2. 2.Institute of Metabolic Disease, Baylor Research InstituteDallasUSA
  3. 3.Clinical and Translational Science Institute, Children’s Hospital Los Angeles, Keck School of MedicineUniversity of Southern CaliforniaLos AngelesUSA

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