{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,5,13]],"date-time":"2025-05-13T15:22:14Z","timestamp":1747149734080,"version":"3.40.5"},"reference-count":31,"publisher":"Wiley","issue":"5","license":[{"start":{"date-parts":[[2023,7,25]],"date-time":"2023-07-25T00:00:00Z","timestamp":1690243200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["JIMD Reports"],"published-print":{"date-parts":[[2023,9]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>Phenylketonuria (PKU) is an autosomal recessive inborn error of metabolism resulting from a deficiency of phenylalanine hydroxylase (PAH). If untreated by dietary restriction of phenylalanine intake, impaired postnatal cognitive development results from the neurotoxic effects of excessive phenylalanine (Phe). Signs and symptoms include severe intellectual disability and behavior problems with a high frequency of seizures and variable microcephaly. Maternal PKU syndrome refers to fetal damage resulting in congenital abnormalities when the mother has untreated PKU during pregnancy. Here, we report an intellectually normal 32\u2010year\u2010old female who presented with recurrent pregnancy loss and two neonatal deaths with congenital heart disease, microcephaly, intrauterine growth restriction, and respiratory distress. She was diagnosed with PKU through exome sequencing performed for carrier testing with a homozygous pathogenic variant in the PAH gene, c.169_171del, p.(Glu57del) that is associated with classical PKU. Consistent with the genetic finding, she had a markedly increased plasma phenylalanine concentration of 1642 \u03bcmol\/L (normal &lt;100). This case demonstrates that recurrent pregnancy loss due to untreated maternal PKU may present as an initial finding in otherwise unsuspected classical PKU and illustrates that extreme degrees of variable expressivity may occur in classical PKU. Moreover, this case illustrates the value of genomic sequencing of women who experience recurrent pregnancy loss or neonatal anomalies.<\/jats:p>","DOI":"10.1002\/jmd2.12384","type":"journal-article","created":{"date-parts":[[2023,7,26]],"date-time":"2023-07-26T05:00:59Z","timestamp":1690347659000},"page":"312-316","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":3,"title":["Classical phenylketonuria presenting as maternal <scp>PKU<\/scp> syndrome in the offspring of an intellectually normal woman"],"prefix":"10.1002","volume":"64","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-8317-5951","authenticated-orcid":false,"given":"Malak Ali","family":"Alghamdi","sequence":"first","affiliation":[{"name":"Harvard Medical School  Boston Massachusetts USA"},{"name":"Medical Genetic Division, Pediatric Department College of Medicine, King Saud University  Riyadh Saudi Arabia"},{"name":"Program in Medical and Population Genetics Broad Institute of MIT and Harvard  Cambridge Massachusetts USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Anne","family":"O'Donnell\u2010Luria","sequence":"additional","affiliation":[{"name":"Harvard Medical School  Boston Massachusetts USA"},{"name":"Program in Medical and Population Genetics Broad Institute of MIT and Harvard  Cambridge Massachusetts USA"},{"name":"Division of Genetics and Genomics Boston Children's Hospital  Boston Massachusetts USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Naif A.","family":"Almontashiri","sequence":"additional","affiliation":[{"name":"Center for Genetics and Inherited Diseases (CGID) Taibah University  Madinah Saudi Arabia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Wajeih Y.","family":"AlAali","sequence":"additional","affiliation":[{"name":"Dr. Sulaiman Al Habib Medical Group Arryan Hospital  Riyadh Saudi Arabia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Hebatallah H.","family":"Ali","sequence":"additional","affiliation":[{"name":"Research Center, College of Medicine King Saud University  Riyadh Saudi Arabia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Harvey L.","family":"Levy","sequence":"additional","affiliation":[{"name":"Harvard Medical School  Boston Massachusetts USA"},{"name":"Program in Medical and Population Genetics Broad Institute of MIT and Harvard  Cambridge Massachusetts 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