Diagnostic pitfalls in vitamin B6‐dependent epilepsy caused by mutations in the PLPBP gene
Abstract Vitamin B6‐responsive epilepsies are a group of genetic disorders including ALDH7A1 deficiency, PNPO deficiency, and others, usually causing neonatal onset seizures resistant to treatment with common antiepileptic drugs. Recently, biallelic mutations in PLPBP were shown to be a novel cause...
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doaj-6ef32b628603403996d5678dc7deb0ae2020-11-25T02:51:32ZengWileyJIMD Reports2192-83122019-11-015011810.1002/jmd2.12063Diagnostic pitfalls in vitamin B6‐dependent epilepsy caused by mutations in the PLPBP geneKristian Vestergaard Jensen0Maria Frid1Tommy Stödberg2Michela Barbaro3Anna Wedell4Mette Christensen5Mads Bak6Jakob Ek7Camilla Gøbel Madsen8Niklas Darin9Sabine Grønborg10Department of Neonatology Copenhagen University Hospital Copenhagen DenmarkDepartment of Paediatrics Ryhov County Hospital Jönköping SwedenDepartment of Women's and Children's Health Karolinska Institutet Stockholm SwedenCentre for Inherited Metabolic Diseases Karolinska University Hospital Stockholm SwedenCentre for Inherited Metabolic Diseases Karolinska University Hospital Stockholm SwedenDepartment of Clinical Genetics Copenhagen University Hospital Copenhagen DenmarkDepartment of Clinical Genetics Copenhagen University Hospital Copenhagen DenmarkDepartment of Clinical Genetics Copenhagen University Hospital Copenhagen DenmarkDepartment of Radiology, Centre for Functional and Diagnostic Imaging and Research Copenhagen University, Hvidovre Hospital Hvidovre DenmarkDepartment of Pediatrics University of Gothenburg, Sahlgrenska University Hospital Gothenburg SwedenDepartment of Clinical Genetics Copenhagen University Hospital Copenhagen DenmarkAbstract Vitamin B6‐responsive epilepsies are a group of genetic disorders including ALDH7A1 deficiency, PNPO deficiency, and others, usually causing neonatal onset seizures resistant to treatment with common antiepileptic drugs. Recently, biallelic mutations in PLPBP were shown to be a novel cause of vitamin B6‐dependent epilepsy with a variable phenotype. The different vitamin B6‐responsive epilepsies can be detected and distinguished by their respective biomarkers and genetic analysis. Unfortunately, metabolic biomarkers for early detection and prognosis of PLPBP deficiency are currently still lacking. Here, we present data from two further patients with vitamin B6‐dependent seizures caused by variants in PLPBP, including a novel missense variant, and compare their genotype and phenotypic presentation to previously described cases. Hyperglycinemia and hyperlactatemia are the most consistently observed biochemical abnormalities in pyridoxal phosphate homeostasis protein (PLPHP) deficient patients and were present in both patients in this report within the first days of life. Lactic acidemia, the neuroradiological, and clinical presentation led to misdiagnosis of a mitochondrial encephalopathy in two previously published cases with an early fatal course. Similarly, on the background of glycine elevation in plasma, glycine encephalopathy was wrongly adopted as diagnosis for a patient in our report. In this regard, lactic acidemia as well as hyperglycinemia appear to be diagnostic pitfalls in patients with vitamin B6‐responsive epilepsies, including PLPHP deficiency. Synopsis In vitamin B6‐responsive epilepsies, including PLPHP deficiency, there are several diagnostic pitfalls, including lactic acidemia as well as hyperglycinemia, highlighting the importance of a pyridoxine trial, and genetic testing.https://doi.org/10.1002/jmd2.12063neonatal seizuresPLPBPPLPHPPROSCpyridoxinevitamin B6‐dependent epilepsy |
collection |
DOAJ |
language |
English |
format |
Article |
sources |
DOAJ |
author |
Kristian Vestergaard Jensen Maria Frid Tommy Stödberg Michela Barbaro Anna Wedell Mette Christensen Mads Bak Jakob Ek Camilla Gøbel Madsen Niklas Darin Sabine Grønborg |
spellingShingle |
Kristian Vestergaard Jensen Maria Frid Tommy Stödberg Michela Barbaro Anna Wedell Mette Christensen Mads Bak Jakob Ek Camilla Gøbel Madsen Niklas Darin Sabine Grønborg Diagnostic pitfalls in vitamin B6‐dependent epilepsy caused by mutations in the PLPBP gene JIMD Reports neonatal seizures PLPBP PLPHP PROSC pyridoxine vitamin B6‐dependent epilepsy |
author_facet |
Kristian Vestergaard Jensen Maria Frid Tommy Stödberg Michela Barbaro Anna Wedell Mette Christensen Mads Bak Jakob Ek Camilla Gøbel Madsen Niklas Darin Sabine Grønborg |
author_sort |
Kristian Vestergaard Jensen |
title |
Diagnostic pitfalls in vitamin B6‐dependent epilepsy caused by mutations in the PLPBP gene |
title_short |
Diagnostic pitfalls in vitamin B6‐dependent epilepsy caused by mutations in the PLPBP gene |
title_full |
Diagnostic pitfalls in vitamin B6‐dependent epilepsy caused by mutations in the PLPBP gene |
title_fullStr |
Diagnostic pitfalls in vitamin B6‐dependent epilepsy caused by mutations in the PLPBP gene |
title_full_unstemmed |
Diagnostic pitfalls in vitamin B6‐dependent epilepsy caused by mutations in the PLPBP gene |
title_sort |
diagnostic pitfalls in vitamin b6‐dependent epilepsy caused by mutations in the plpbp gene |
publisher |
Wiley |
series |
JIMD Reports |
issn |
2192-8312 |
publishDate |
2019-11-01 |
description |
Abstract Vitamin B6‐responsive epilepsies are a group of genetic disorders including ALDH7A1 deficiency, PNPO deficiency, and others, usually causing neonatal onset seizures resistant to treatment with common antiepileptic drugs. Recently, biallelic mutations in PLPBP were shown to be a novel cause of vitamin B6‐dependent epilepsy with a variable phenotype. The different vitamin B6‐responsive epilepsies can be detected and distinguished by their respective biomarkers and genetic analysis. Unfortunately, metabolic biomarkers for early detection and prognosis of PLPBP deficiency are currently still lacking. Here, we present data from two further patients with vitamin B6‐dependent seizures caused by variants in PLPBP, including a novel missense variant, and compare their genotype and phenotypic presentation to previously described cases. Hyperglycinemia and hyperlactatemia are the most consistently observed biochemical abnormalities in pyridoxal phosphate homeostasis protein (PLPHP) deficient patients and were present in both patients in this report within the first days of life. Lactic acidemia, the neuroradiological, and clinical presentation led to misdiagnosis of a mitochondrial encephalopathy in two previously published cases with an early fatal course. Similarly, on the background of glycine elevation in plasma, glycine encephalopathy was wrongly adopted as diagnosis for a patient in our report. In this regard, lactic acidemia as well as hyperglycinemia appear to be diagnostic pitfalls in patients with vitamin B6‐responsive epilepsies, including PLPHP deficiency. Synopsis In vitamin B6‐responsive epilepsies, including PLPHP deficiency, there are several diagnostic pitfalls, including lactic acidemia as well as hyperglycinemia, highlighting the importance of a pyridoxine trial, and genetic testing. |
topic |
neonatal seizures PLPBP PLPHP PROSC pyridoxine vitamin B6‐dependent epilepsy |
url |
https://doi.org/10.1002/jmd2.12063 |
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