Classical phenylketonuria presenting as maternal PKU syndrome in the offspring of an intellectually normal woman
Abstract 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 p...
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| Format: | Article |
| Language: | English |
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Wiley
2023-09-01
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| Series: | JIMD Reports |
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| Online Access: | https://doi.org/10.1002/jmd2.12384 |
| _version_ | 1797690220702859264 |
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| author | Malak Ali Alghamdi Anne O'Donnell‐Luria Naif A. Almontashiri Wajeih Y. AlAali Hebatallah H. Ali Harvey L. Levy |
| author_facet | Malak Ali Alghamdi Anne O'Donnell‐Luria Naif A. Almontashiri Wajeih Y. AlAali Hebatallah H. Ali Harvey L. Levy |
| author_sort | Malak Ali Alghamdi |
| collection | DOAJ |
| description | Abstract 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‐year‐old 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 μmol/L (normal <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. |
| first_indexed | 2024-03-12T01:56:24Z |
| format | Article |
| id | doaj.art-a5750c53bc33416db906f5d4a48ad006 |
| institution | Directory Open Access Journal |
| issn | 2192-8312 |
| language | English |
| last_indexed | 2024-03-12T01:56:24Z |
| publishDate | 2023-09-01 |
| publisher | Wiley |
| record_format | Article |
| series | JIMD Reports |
| spelling | doaj.art-a5750c53bc33416db906f5d4a48ad0062023-09-08T04:48:16ZengWileyJIMD Reports2192-83122023-09-0164531231610.1002/jmd2.12384Classical phenylketonuria presenting as maternal PKU syndrome in the offspring of an intellectually normal womanMalak Ali Alghamdi0Anne O'Donnell‐Luria1Naif A. Almontashiri2Wajeih Y. AlAali3Hebatallah H. Ali4Harvey L. Levy5Harvard Medical School Boston Massachusetts USAHarvard Medical School Boston Massachusetts USACenter for Genetics and Inherited Diseases (CGID) Taibah University Madinah Saudi ArabiaDr. Sulaiman Al Habib Medical Group Arryan Hospital Riyadh Saudi ArabiaResearch Center, College of Medicine King Saud University Riyadh Saudi ArabiaHarvard Medical School Boston Massachusetts USAAbstract 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‐year‐old 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 μmol/L (normal <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.https://doi.org/10.1002/jmd2.12384maternal PKU syndromeneonatal deathsphenylalanine hydroxylaserecurrent pregnancy lossvariable expressivity |
| spellingShingle | Malak Ali Alghamdi Anne O'Donnell‐Luria Naif A. Almontashiri Wajeih Y. AlAali Hebatallah H. Ali Harvey L. Levy Classical phenylketonuria presenting as maternal PKU syndrome in the offspring of an intellectually normal woman JIMD Reports maternal PKU syndrome neonatal deaths phenylalanine hydroxylase recurrent pregnancy loss variable expressivity |
| title | Classical phenylketonuria presenting as maternal PKU syndrome in the offspring of an intellectually normal woman |
| title_full | Classical phenylketonuria presenting as maternal PKU syndrome in the offspring of an intellectually normal woman |
| title_fullStr | Classical phenylketonuria presenting as maternal PKU syndrome in the offspring of an intellectually normal woman |
| title_full_unstemmed | Classical phenylketonuria presenting as maternal PKU syndrome in the offspring of an intellectually normal woman |
| title_short | Classical phenylketonuria presenting as maternal PKU syndrome in the offspring of an intellectually normal woman |
| title_sort | classical phenylketonuria presenting as maternal pku syndrome in the offspring of an intellectually normal woman |
| topic | maternal PKU syndrome neonatal deaths phenylalanine hydroxylase recurrent pregnancy loss variable expressivity |
| url | https://doi.org/10.1002/jmd2.12384 |
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