{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,18]],"date-time":"2026-08-18T04:49:40Z","timestamp":1787028580598,"version":"build-2736575974"},"reference-count":27,"publisher":"MDPI AG","issue":"9","license":[{"start":{"date-parts":[[2026,4,29]],"date-time":"2026-04-29T00:00:00Z","timestamp":1777420800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"European Union-NextGenerationEU","award":["No BG-RRP-2.004- 0007-C03"],"award-info":[{"award-number":["No BG-RRP-2.004- 0007-C03"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>The C-terminal binding protein 1 (CTBP1) is a transcriptional corepressor with a major role in nervous system growth and development. There are only 20 published cases with CTBP1 mutations, displaying a phenotype of Hypotonia, Ataxia, Developmental Delay and Tooth enamel defect Syndrome (HADDTS). Histochemical evidence of decreased mitochondrial respiratory chain activity has been previously reported, but comprehensive data on the metabolic phenotype assessed by various cellular respiration parameters are still missing. We present a 10-year-old female with typical HADDTS features, harboring the most reported de novo heterozygous CTBP1 mutation c.991C&gt;T. To elucidate her metabolic phenotype, we quantified mitochondrial respiration in peripheral blood mononuclear cells (PBMCs) utilizing an analyzer for assessing mitochondrial function (Seahorse XFp). Real-time metabolic assays revealed profound mitochondrial dysfunction with significantly attenuated maximal respiration and spare respiratory capacity compared to neurotypical controls. Following mitochondria-targeted nutritional support for one-year measurable bioenergetic improvements and reduced number of respiratory infections were registered. However, neurological recovery and new skill acquisition were not observed. We present a novel case of CTBP1-related neurodevelopmental disorder and demonstrate, for the first time, the application of non-invasive, real-time mitochondrial functional assessment in this setting, providing additional evidence for mitochondrial dysfunction in HADDTS.<\/jats:p>","DOI":"10.3390\/ijms27094003","type":"journal-article","created":{"date-parts":[[2026,4,30]],"date-time":"2026-04-30T08:03:47Z","timestamp":1777536227000},"page":"4003","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["A Rare CTBP1-Related Neurodevelopmental Disorder Is Associated with Impaired Mitochondrial Bioenergetics: A Functional Case Report"],"prefix":"10.3390","volume":"27","author":[{"ORCID":"https:\/\/orcid.org\/0009-0004-2659-9696","authenticated-orcid":false,"given":"Zdravko","family":"Ivanov","sequence":"first","affiliation":[{"name":"Pediatrics Clinic, St. George University Hospital, 4002 Plovdiv, Bulgaria"},{"name":"Department of Pediatrics, Medical University of Plovdiv, 4002 Plovdiv, Bulgaria"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Maria","family":"Gevezova","sequence":"additional","affiliation":[{"name":"Department of Medical Biology, Medical University of Plovdiv, 4002 Plovdiv, Bulgaria"},{"name":"Research Institute at Medical University of Plovdiv, 4002 Plovdiv, Bulgaria"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Iliyana","family":"Pacheva","sequence":"additional","affiliation":[{"name":"Pediatrics Clinic, St. George University Hospital, 4002 Plovdiv, Bulgaria"},{"name":"Research Institute at Medical University of Plovdiv, 4002 Plovdiv, Bulgaria"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5395-9125","authenticated-orcid":false,"given":"Kostadin","family":"Ketev","sequence":"additional","affiliation":[{"name":"Pediatrics Clinic, St. George University Hospital, 4002 Plovdiv, Bulgaria"},{"name":"Medical Simulation Training Center, Medical University of Plovdiv, 4002 Plovdiv, Bulgaria"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lyubov","family":"Chochkova-Bukova","sequence":"additional","affiliation":[{"name":"Pediatrics Clinic, St. George University Hospital, 4002 Plovdiv, Bulgaria"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1501-0175","authenticated-orcid":false,"given":"Victoria","family":"Sarafian","sequence":"additional","affiliation":[{"name":"Department of Medical Biology, Medical University of Plovdiv, 4002 Plovdiv, Bulgaria"},{"name":"Research Institute at Medical University of Plovdiv, 4002 Plovdiv, Bulgaria"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ivan","family":"Ivanov","sequence":"additional","affiliation":[{"name":"Pediatrics Clinic, St. George University Hospital, 4002 Plovdiv, Bulgaria"},{"name":"Department of Pediatrics, Medical University of Plovdiv, 4002 Plovdiv, Bulgaria"},{"name":"Research Institute at Medical University of Plovdiv, 4002 Plovdiv, Bulgaria"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2026,4,29]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"231","DOI":"10.1007\/s10048-022-00700-w","article-title":"CTBP1 and CTBP2 mutations underpinning neurological disorders: A systematic review","volume":"23","year":"2022","journal-title":"Neurogenetics"},{"key":"ref_2","first-page":"546","article-title":"Mitochondrial respiratory chain dysfunction in a patient with a heterozygous de novo CTBP1 variant","volume":"63","author":"Wong","year":"2022","journal-title":"JIMD Rep."},{"key":"ref_3","doi-asserted-by":"crossref","unstructured":"Zhang, Q., Liu, Y., Liu, X., Zhao, Y., and Zhang, J. 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