Partial N‐acetyl glutamate synthase deficiency presenting as postpartum hyperammonemia: Diagnosis and subsequent pregnancy management
Abstract N‐acetyl glutamate synthase (NAGS) deficiency (OMIM #: 237310) is a rare urea cycle disorder that usually presents early in life with hyperammonemia. NAGS catalyzes the synthesis of N‐acetyl glutamate (NAG) which functions as an activator of the carbamoyl phosphate synthetase‐1 mediated con...
| Main Authors: | , , , , , |
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| Format: | Article |
| Language: | English |
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Wiley
2023-11-01
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| Series: | JIMD Reports |
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| Online Access: | https://doi.org/10.1002/jmd2.12388 |
| _version_ | 1797640025009029120 |
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| author | Lea Abou Haidar Panayotis Pachnis Garrett K. Gotway Min Ni Ralph J. DeBerardinis Markey C. McNutt |
| author_facet | Lea Abou Haidar Panayotis Pachnis Garrett K. Gotway Min Ni Ralph J. DeBerardinis Markey C. McNutt |
| author_sort | Lea Abou Haidar |
| collection | DOAJ |
| description | Abstract N‐acetyl glutamate synthase (NAGS) deficiency (OMIM #: 237310) is a rare urea cycle disorder that usually presents early in life with hyperammonemia. NAGS catalyzes the synthesis of N‐acetyl glutamate (NAG) which functions as an activator of the carbamoyl phosphate synthetase‐1 mediated conversion of ammonia to carbamoyl phosphate. The absence of NAG results in a proximal urea cycle disorder which can result in severe neurologic sequelae secondary to hyperammonemia and even death. Unlike the other urea cycle disorders, a specific pharmacological treatment for NAGS deficiency exists in the form of carglumic acid, an analog of NAG. Here we present a 29‐year‐old previously healthy female who presented with hyperammonemia and obtundation just after the birth of her first child. Exome sequencing revealed two novel variants in the NAGS gene, and plasma metabolomics revealed extremely low levels of NAG. Carglumic acid treatment led to prompt resolution of her biochemical abnormalities and symptoms. She tolerated two subsequent pregnancies, 2 years and 6 years after her initial presentation, while taking carglumic acid, and breastfed her third child, all without complications in the mother or children. This case report emphasizes the importance of considering urea cycle disorders in previously‐healthy adults presenting with neurological symptoms during periods of metabolic stress, including the postpartum period. It also highlights the efficacious and safe use of carglumic acid during pregnancy and while breastfeeding. |
| first_indexed | 2024-03-11T13:26:00Z |
| format | Article |
| id | doaj.art-f478348a0d3a4ecbad4d0dbf8afb2b97 |
| institution | Directory Open Access Journal |
| issn | 2192-8312 |
| language | English |
| last_indexed | 2024-03-11T13:26:00Z |
| publishDate | 2023-11-01 |
| publisher | Wiley |
| record_format | Article |
| series | JIMD Reports |
| spelling | doaj.art-f478348a0d3a4ecbad4d0dbf8afb2b972023-11-03T07:45:49ZengWileyJIMD Reports2192-83122023-11-0164640340910.1002/jmd2.12388Partial N‐acetyl glutamate synthase deficiency presenting as postpartum hyperammonemia: Diagnosis and subsequent pregnancy managementLea Abou Haidar0Panayotis Pachnis1Garrett K. Gotway2Min Ni3Ralph J. DeBerardinis4Markey C. McNutt5Children's Medical Center Research Institute The University of Texas Southwestern Medical Center Dallas Texas USAChildren's Medical Center Research Institute The University of Texas Southwestern Medical Center Dallas Texas USADepartment of Pediatrics The University of Texas Southwestern Medical Center Dallas Texas USAChildren's Medical Center Research Institute The University of Texas Southwestern Medical Center Dallas Texas USAChildren's Medical Center Research Institute The University of Texas Southwestern Medical Center Dallas Texas USADepartment of Pediatrics The University of Texas Southwestern Medical Center Dallas Texas USAAbstract N‐acetyl glutamate synthase (NAGS) deficiency (OMIM #: 237310) is a rare urea cycle disorder that usually presents early in life with hyperammonemia. NAGS catalyzes the synthesis of N‐acetyl glutamate (NAG) which functions as an activator of the carbamoyl phosphate synthetase‐1 mediated conversion of ammonia to carbamoyl phosphate. The absence of NAG results in a proximal urea cycle disorder which can result in severe neurologic sequelae secondary to hyperammonemia and even death. Unlike the other urea cycle disorders, a specific pharmacological treatment for NAGS deficiency exists in the form of carglumic acid, an analog of NAG. Here we present a 29‐year‐old previously healthy female who presented with hyperammonemia and obtundation just after the birth of her first child. Exome sequencing revealed two novel variants in the NAGS gene, and plasma metabolomics revealed extremely low levels of NAG. Carglumic acid treatment led to prompt resolution of her biochemical abnormalities and symptoms. She tolerated two subsequent pregnancies, 2 years and 6 years after her initial presentation, while taking carglumic acid, and breastfed her third child, all without complications in the mother or children. This case report emphasizes the importance of considering urea cycle disorders in previously‐healthy adults presenting with neurological symptoms during periods of metabolic stress, including the postpartum period. It also highlights the efficacious and safe use of carglumic acid during pregnancy and while breastfeeding.https://doi.org/10.1002/jmd2.12388carglumic acidhyperammonemialactationN‐acetyl glutamate synthase deficiencypregnancyurea cycle disorders |
| spellingShingle | Lea Abou Haidar Panayotis Pachnis Garrett K. Gotway Min Ni Ralph J. DeBerardinis Markey C. McNutt Partial N‐acetyl glutamate synthase deficiency presenting as postpartum hyperammonemia: Diagnosis and subsequent pregnancy management JIMD Reports carglumic acid hyperammonemia lactation N‐acetyl glutamate synthase deficiency pregnancy urea cycle disorders |
| title | Partial N‐acetyl glutamate synthase deficiency presenting as postpartum hyperammonemia: Diagnosis and subsequent pregnancy management |
| title_full | Partial N‐acetyl glutamate synthase deficiency presenting as postpartum hyperammonemia: Diagnosis and subsequent pregnancy management |
| title_fullStr | Partial N‐acetyl glutamate synthase deficiency presenting as postpartum hyperammonemia: Diagnosis and subsequent pregnancy management |
| title_full_unstemmed | Partial N‐acetyl glutamate synthase deficiency presenting as postpartum hyperammonemia: Diagnosis and subsequent pregnancy management |
| title_short | Partial N‐acetyl glutamate synthase deficiency presenting as postpartum hyperammonemia: Diagnosis and subsequent pregnancy management |
| title_sort | partial n acetyl glutamate synthase deficiency presenting as postpartum hyperammonemia diagnosis and subsequent pregnancy management |
| topic | carglumic acid hyperammonemia lactation N‐acetyl glutamate synthase deficiency pregnancy urea cycle disorders |
| url | https://doi.org/10.1002/jmd2.12388 |
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