{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,20]],"date-time":"2026-10-20T10:10:08Z","timestamp":1792491008967,"version":"4.5.0"},"reference-count":95,"publisher":"Wiley","issue":"5","license":[{"start":{"date-parts":[[2026,8,15]],"date-time":"2026-08-15T00:00:00Z","timestamp":1786752000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2026,8,15]],"date-time":"2026-08-15T00:00:00Z","timestamp":1786752000000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"funder":[{"DOI":"10.13039\/501100011906","name":"Bayerische Forschungsallianz","doi-asserted-by":"publisher","award":["BayIntAn_TUM_MRI_2025_03"],"award-info":[{"award-number":["BayIntAn_TUM_MRI_2025_03"]}],"id":[{"id":"10.13039\/501100011906","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["J of Inher Metab Disea"],"published-print":{"date-parts":[[2026,9]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:p>\n                    Coenzyme A (CoA) biosynthesis is a conserved, dynamically regulated pathway essential for mitochondrial energy production, fatty acid oxidation, lipid biosynthesis and protein acylation. Biallelic variants in\n                    <jats:italic>PANK2<\/jats:italic>\n                    ,\n                    <jats:italic>PPCS<\/jats:italic>\n                    ,\n                    <jats:italic>PPCDC<\/jats:italic>\n                    , and\n                    <jats:italic>COASY<\/jats:italic>\n                    cause rare inborn errors of CoA biosynthesis, associated with markedly different clinical phenotypes:\n                    <jats:italic>PANK2<\/jats:italic>\n                    and\n                    <jats:italic>COASY<\/jats:italic>\n                    defects predominantly cause neurological disorders within or adjacent to the neurodegeneration with brain iron accumulation (NBIA) spectrum, whereas\n                    <jats:italic>PPCS<\/jats:italic>\n                    and\n                    <jats:italic>PPCDC<\/jats:italic>\n                    deficiencies present mainly as severe early\u2010onset dilated cardiomyopathy. However,\n                    <jats:italic>COASY<\/jats:italic>\n                    variants can also cause pontocerebellar hypoplasia and riboflavin\u2010responsive lipid storage myopathy. This review examines these four disorders from a metabolic perspective, integrating clinical features, experimental models, biochemical data and emerging therapeutic approaches. Current evidence indicates that disease pathogenesis cannot be explained only by global CoA depletion. Total CoA levels may be reduced in\n                    <jats:italic>PPCS<\/jats:italic>\n                    and\n                    <jats:italic>PPCDC<\/jats:italic>\n                    deficiency, but are often preserved under basal conditions in PKAN and COASY\u2010related models. Instead, impaired compartment\u2010specific CoA handling and failure to sustain CoA\u2010dependent flux under increased metabolic demand are emerging as central pathogenic concepts. Perturbation of fatty acid handling, acyl\u2010CoA\/acylcarnitine balance, mitochondrial function, iron homeostasis, protein acylation and 4\u2032\u2010phosphopantetheinylation may contribute to tissue\u2010selective vulnerability. Therapeutic strategies are therefore likely to require disease\u2010specific approaches, including precursor bypass or PANK activation where pathway flux can be restored, early pantethine supplementation in cardiomyopathic forms, and downstream or gene\u2010directed strategies for COASY\u2010related disorders. Understanding CoA as a regulator of metabolic adaptability provides a unifying framework for interpreting both shared mechanisms and disease divergence.\n                  <\/jats:p>","DOI":"10.1002\/jimd.70239","type":"journal-article","created":{"date-parts":[[2026,8,15]],"date-time":"2026-08-15T07:26:01Z","timestamp":1786778761000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["From Common Pathway to Divergent Diseases: Metabolic Aspects of Inborn Errors of\n                    <scp>CoA<\/scp>\n                    Biosynthesis"],"prefix":"10.1002","volume":"49","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-4616-5623","authenticated-orcid":false,"given":"Ivano","family":"Di Meo","sequence":"first","affiliation":[{"name":"Unit of Medical Genetics and Neurogenetics Fondazione IRCCS Istituto Neurologico Carlo Besta  Milan Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2157-273X","authenticated-orcid":false,"given":"Yair","family":"Anikster","sequence":"additional","affiliation":[{"name":"Gray Faculty of Medical and Health Sciences Tel Aviv University  Tel Aviv Israel"},{"name":"Metabolic Disease Unit Edmond and Lily Safra Children's Hospital, Sheba Medical Center  Ramat Gan Israel"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3584-7338","authenticated-orcid":false,"given":"Valeria","family":"Tiranti","sequence":"additional","affiliation":[{"name":"Unit of Medical Genetics and Neurogenetics Fondazione IRCCS Istituto Neurologico Carlo Besta  Milan Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4844-2513","authenticated-orcid":false,"given":"Arcangela","family":"Iuso","sequence":"additional","affiliation":[{"name":"Institute of Neurogenomics, Helmholtz Zentrum M\u00fcnchen  Neuherberg Germany"},{"name":"Institute of Human Genetics, School of Medicine and Health Technical University of Munich  Munich 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