Early‐onset vitamin B6‐dependent epilepsy due to pathogenic PLPBP variants in a premature infant: A case report and review of the literature
Abstract Vitamin B6‐dependent epilepsies are a heterogeneous group of disorders characterized by decreased availability of the active cofactor pyridoxal‐5′‐phosphate (PLP). While pathogenic variants in ALDH7A1 or PNPO genes account for most cases of these disorders, biallelic pathogenic variants in...
| Main Authors: | , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
Wiley
2021-03-01
|
| Series: | JIMD Reports |
| Subjects: | |
| Online Access: | https://doi.org/10.1002/jmd2.12183 |
| _version_ | 1818728501417607168 |
|---|---|
| author | Oliver Heath James Pitt Simone Mandelstam Carl Kuschel Anand Vasudevan Sarah Donoghue |
| author_facet | Oliver Heath James Pitt Simone Mandelstam Carl Kuschel Anand Vasudevan Sarah Donoghue |
| author_sort | Oliver Heath |
| collection | DOAJ |
| description | Abstract Vitamin B6‐dependent epilepsies are a heterogeneous group of disorders characterized by decreased availability of the active cofactor pyridoxal‐5′‐phosphate (PLP). While pathogenic variants in ALDH7A1 or PNPO genes account for most cases of these disorders, biallelic pathogenic variants in PLPBP have been shown to cause a form of early onset vitamin B6‐dependent epilepsy (EPVB6D). PLPBP is thought to play a role in the homeostatic regulation of vitamin B6, by supplying PLP to apoenzymes while limiting side‐reaction toxicity related to excess unbound PLP. Neonatal‐onset intractable seizures that respond to pyridoxine and/or PLP are a predominant feature of EPVB6D in humans. Unlike other causes of vitamin B6‐dependent epilepsies; however, a specific biomarker for this disorder has yet to be identified. Here we present data from a premature infant found to have pathogenic variants in PLPBP and propose that prematurity may provide an additional clue for early consideration of this diagnosis. We discuss these findings in context of previously published genotypic, phenotypic, and metabolic data from similarly affected patients. |
| first_indexed | 2024-12-17T22:31:00Z |
| format | Article |
| id | doaj.art-df2e74638e0841458165745a0241ed55 |
| institution | Directory Open Access Journal |
| issn | 2192-8312 |
| language | English |
| last_indexed | 2024-12-17T22:31:00Z |
| publishDate | 2021-03-01 |
| publisher | Wiley |
| record_format | Article |
| series | JIMD Reports |
| spelling | doaj.art-df2e74638e0841458165745a0241ed552022-12-21T21:30:12ZengWileyJIMD Reports2192-83122021-03-0158131110.1002/jmd2.12183Early‐onset vitamin B6‐dependent epilepsy due to pathogenic PLPBP variants in a premature infant: A case report and review of the literatureOliver Heath0James Pitt1Simone Mandelstam2Carl Kuschel3Anand Vasudevan4Sarah Donoghue5Department of Metabolic Medicine The Royal Children's Hospital Melbourne AustraliaDepartment of Biochemical Genetics, Victorian Clinical Genetics Service Murdoch Children's Research Institute Melbourne AustraliaDepartment of Medical Imaging The Royal Children's Hospital and Murdoch Children's Research Institute Melbourne AustraliaDepartment of Obstetrics and Gynecology The Royal Women's Hospital Melbourne AustraliaDepartment of Genetics The Royal Women's Hospital Melbourne AustraliaDepartment of Metabolic Medicine The Royal Children's Hospital Melbourne AustraliaAbstract Vitamin B6‐dependent epilepsies are a heterogeneous group of disorders characterized by decreased availability of the active cofactor pyridoxal‐5′‐phosphate (PLP). While pathogenic variants in ALDH7A1 or PNPO genes account for most cases of these disorders, biallelic pathogenic variants in PLPBP have been shown to cause a form of early onset vitamin B6‐dependent epilepsy (EPVB6D). PLPBP is thought to play a role in the homeostatic regulation of vitamin B6, by supplying PLP to apoenzymes while limiting side‐reaction toxicity related to excess unbound PLP. Neonatal‐onset intractable seizures that respond to pyridoxine and/or PLP are a predominant feature of EPVB6D in humans. Unlike other causes of vitamin B6‐dependent epilepsies; however, a specific biomarker for this disorder has yet to be identified. Here we present data from a premature infant found to have pathogenic variants in PLPBP and propose that prematurity may provide an additional clue for early consideration of this diagnosis. We discuss these findings in context of previously published genotypic, phenotypic, and metabolic data from similarly affected patients.https://doi.org/10.1002/jmd2.12183PLPBPPLPHPprematurityPROSCpyridoxal‐5′‐phosphatepyridoxine |
| spellingShingle | Oliver Heath James Pitt Simone Mandelstam Carl Kuschel Anand Vasudevan Sarah Donoghue Early‐onset vitamin B6‐dependent epilepsy due to pathogenic PLPBP variants in a premature infant: A case report and review of the literature JIMD Reports PLPBP PLPHP prematurity PROSC pyridoxal‐5′‐phosphate pyridoxine |
| title | Early‐onset vitamin B6‐dependent epilepsy due to pathogenic PLPBP variants in a premature infant: A case report and review of the literature |
| title_full | Early‐onset vitamin B6‐dependent epilepsy due to pathogenic PLPBP variants in a premature infant: A case report and review of the literature |
| title_fullStr | Early‐onset vitamin B6‐dependent epilepsy due to pathogenic PLPBP variants in a premature infant: A case report and review of the literature |
| title_full_unstemmed | Early‐onset vitamin B6‐dependent epilepsy due to pathogenic PLPBP variants in a premature infant: A case report and review of the literature |
| title_short | Early‐onset vitamin B6‐dependent epilepsy due to pathogenic PLPBP variants in a premature infant: A case report and review of the literature |
| title_sort | early onset vitamin b6 dependent epilepsy due to pathogenic plpbp variants in a premature infant a case report and review of the literature |
| topic | PLPBP PLPHP prematurity PROSC pyridoxal‐5′‐phosphate pyridoxine |
| url | https://doi.org/10.1002/jmd2.12183 |
| work_keys_str_mv | AT oliverheath earlyonsetvitaminb6dependentepilepsyduetopathogenicplpbpvariantsinaprematureinfantacasereportandreviewoftheliterature AT jamespitt earlyonsetvitaminb6dependentepilepsyduetopathogenicplpbpvariantsinaprematureinfantacasereportandreviewoftheliterature AT simonemandelstam earlyonsetvitaminb6dependentepilepsyduetopathogenicplpbpvariantsinaprematureinfantacasereportandreviewoftheliterature AT carlkuschel earlyonsetvitaminb6dependentepilepsyduetopathogenicplpbpvariantsinaprematureinfantacasereportandreviewoftheliterature AT anandvasudevan earlyonsetvitaminb6dependentepilepsyduetopathogenicplpbpvariantsinaprematureinfantacasereportandreviewoftheliterature AT sarahdonoghue earlyonsetvitaminb6dependentepilepsyduetopathogenicplpbpvariantsinaprematureinfantacasereportandreviewoftheliterature |