1. Case report: Early (molecular) diagnosis is the clue: report on ALDH7A1 deficiency in newborns.
- Author
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Lipiński, Patryk, Wójcicka-Kowalczyk, Katarzyna, Bogdańska, Anna, Ehmke, Ewa, Pajdowska, Magdalena, Skrzypek, Katarzyna, Charzewska, Agnieszka, and Hoffman-Zacharska, Dorota
- Subjects
GENETIC testing ,PIPECOLIC acid ,NUCLEOTIDE sequencing ,RF values (Chromatography) ,GENETIC variation - Abstract
The first-tier genetic 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. In addition to the fact that biochemical biomarkers of PDE-ALDH7A1, including a-aminoadipic semialdehyde dehydrogenase, pipecolic acid (PA), 1-piperideine-6-carboxylate, and 6-oxopipecolate (6-oxo-PIP), are well-characterized, and their analysis and usefulness have some limitations. Here, we describe the case of a newborn presenting with seizures from the first hours of life, who was resistant to standard antiepileptic drugs and was found to be a biallelic compound heterozygote of two clearly pathogenic variants in the 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 the 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. [ABSTRACT FROM AUTHOR]
- Published
- 2024
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