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It arises as a result of damaging variants in <jats:italic>ALDH7A1,<\/jats:italic> a gene in the lysine catabolism pathway. \u03b1\u2010Aminoadipic semialdehyde (\u03b1\u2010AASA) and \u0394<jats:sup>1<\/jats:sup>\u2010piperideine\u20106\u2010carboxylate (P6C), which accumulate because of the block in the lysine pathway, are diagnostic biomarkers for this disorder. Recently, it has been reported that 6\u2010oxo\u2010pipecolic acid (6\u2010oxo\u2010PIP) also accumulates in the urine, CSF and plasma of ALDH7A1\u2010deficient individuals and that, given its improved stability, it may be a more suitable biomarker for this disorder. This study measured 6\u2010oxo\u2010PIP in urine from a cohort of 30 patients where \u03b1\u2010AASA was elevated and showed that it was above the normal range in all those above 6\u2009months of age. However, 6\u2010oxo\u2010PIP levels were within the normal range in 33% of the patients below 6\u2009months of age. Levels increased with age and correlated with a decrease in \u03b1\u2010AASA levels. Longitudinal analysis of urine samples from ALDH7A1\u2010deficient patients who were on a lysine restricted diet whilst receiving supraphysiological doses of pyridoxine showed that levels of 6\u2010oxo\u2010PIP remained elevated whilst \u03b1\u2010AASA decreased. Similar to \u03b1\u2010AASA, we found that elevated urinary excretion of 6\u2010oxo\u2010PIP can also occur in individuals with molybdenum cofactor deficiency. This study demonstrates that urinary 6\u2010oxo\u2010PIP may not be a suitable biomarker for ALDH7A1 deficiency in neonates. However, further studies are needed to understand the biochemistry leading to its accumulation and its potential long\u2010term side effects.<\/jats:p>","DOI":"10.1002\/jimd.12783","type":"journal-article","created":{"date-parts":[[2024,7,22]],"date-time":"2024-07-22T20:38:01Z","timestamp":1721680681000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":7,"title":["Assessment of urinary 6\u2010oxo\u2010pipecolic acid as a biomarker for ALDH7A1 deficiency"],"prefix":"10.1002","volume":"48","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-9025-3017","authenticated-orcid":false,"given":"Youssef","family":"Khalil","sequence":"first","affiliation":[{"name":"Genetics and Genomic Medicine University College London Great Ormond Street Institute of Child Health  London UK"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Emma","family":"Footitt","sequence":"additional","affiliation":[{"name":"Department of Metabolic 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