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CASE REPORT article
Front. Genet.
Sec. Genetics of Common and Rare Diseases
Volume 15 - 2024 |
doi: 10.3389/fgene.2024.1464556
Early (molecular) diagnosis is the clue: report on ALDH7A1 deficiency of newborn
Provisionally accepted- 1 Institute of Clinical Sciences, Maria Sklodowska-Curie Medical Academy, Warsaw, Poland
- 2 Children's Memorial Health Institute (IPCZD), Warsaw, Masovian, Poland
- 3 Masdiag, Warsaw, Poland
- 4 Institute of Mother and Child, Warsaw, Masovian, Poland
The first-tier geneting testing for developmental and epileptic encephalopathies (DEE) is now increasingly used in routine clinical practice. Antiquitin deficiency, also referred to as pyridoxine-dependent epilepsy (PDE-ALDH7A1), represents an inherited metabolic disorder with the phenotype of an early-infantile DEE. Besides the fact that biochemical biomarkers of PDE-ALDH7A1, including α-aminoadipic semialdehyde dehydrogenase, pipecolic acid (PA), Δ1-piperideine-6-carboxylate, and 6-oxopipecolate (6-oxo-PIP) are well characterized, their analysis and usefulness have some limitations. Here we describe the case of a newborn presenting with seizures from the first hours of life, resistant to standard antiepileptic drugs, who was found to be a biallelic compound heterozygote of two clearly pathogenic variants in ALDH7A1 gene based on targeted next generation sequencing (NGS). The diagnostic process of PDE-ALDH7A1 was limited by the possibility to determine only urinary PA and 6-oxo-PIP (urinary organic acid profile using GC-MS method) and the exogenous peak of levetiracetam, due to the fact that it has a similar retention time as 6-oxo-PIP, masked the detection of 6-oxo-PIP.
Keywords: Developmental and epileptic encephalopathies, Pyridoxine-dependent epilepsy, 6-oxopipecolate, next generation sequencing, ALDH7A1 gene
Received: 14 Jul 2024; Accepted: 28 Aug 2024.
Copyright: © 2024 Lipiński, Wójcicka-Kowalczyk, Bogdańska, Ehmke, Pajdowska, Skrzypek, Charzewska and Hoffman. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
* Correspondence:
Patryk Lipiński, Institute of Clinical Sciences, Maria Sklodowska-Curie Medical Academy, Warsaw, Poland
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