{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,4,16]],"date-time":"2026-04-16T00:30:18Z","timestamp":1776299418147,"version":"3.50.1"},"reference-count":18,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2022,2,9]],"date-time":"2022-02-09T00:00:00Z","timestamp":1644364800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100005375","name":"Latvijas Zin\u0101tnes Padome","doi-asserted-by":"publisher","award":["lzp-2018\/1-0180"],"award-info":[{"award-number":["lzp-2018\/1-0180"]}],"id":[{"id":"10.13039\/501100005375","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100002301","name":"Eesti Teadusagentuur","doi-asserted-by":"publisher","award":["MOBTP175 PUTJD827"],"award-info":[{"award-number":["MOBTP175 PUTJD827"]}],"id":[{"id":"10.13039\/501100002301","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Genet."],"abstract":"<jats:p>There are recent reports of associations of variants in the <jats:italic>HPDL<\/jats:italic> gene with a hereditary neurological disease that presents with a wide spectrum of clinical severity, ranging from severe neonatal encephalopathy with no psychomotor development to adolescent-onset uncomplicated spastic paraplegia. Here, we report two probands from unrelated families presenting with severe and intermediate variations of the clinical course. A homozygous variant in the <jats:italic>HPDL<\/jats:italic> gene was detected in each proband; however, there was no known parental consanguinity. We also highlight reductions in citrate synthase and mitochondrial complex I activity detected in both probands in different tissues, reflecting the previously proposed mitochondrial nature of disease pathogenesis associated with <jats:italic>HPDL<\/jats:italic> mutations. Further, we speculate on the functional consequences of the detected variants, although the function and substrate of the HPDL enzyme are currently unknown.<\/jats:p>","DOI":"10.3389\/fgene.2022.780764","type":"journal-article","created":{"date-parts":[[2022,2,9]],"date-time":"2022-02-09T06:46:51Z","timestamp":1644389211000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":14,"title":["Case Report: Two Families With HPDL Related Neurodegeneration"],"prefix":"10.3389","volume":"13","author":[{"given":"Ieva","family":"Micule","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Baiba","family":"Lace","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Nathan T.","family":"Wright","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Nicolas","family":"Chrestian","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jurgis","family":"Strautmanis","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Mikus","family":"Diriks","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Janis","family":"Stavusis","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Dita","family":"Kidere","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Elfa","family":"Kleina","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Anna","family":"Zdanovica","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Nataly","family":"Laflamme","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Nadie","family":"Rioux","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Samarth Thonta","family":"Setty","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Sander","family":"Pajusalu","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Arnaud","family":"Droit","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Monkol","family":"Lek","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Serge","family":"Rivest","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Inna","family":"Inashkina","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1965","published-online":{"date-parts":[[2022,2,9]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","first-page":"1396","DOI":"10.1038\/sj.cdd.4401963","article-title":"Mitochondrial Outer Membrane Permeabilization during Apoptosis: the Innocent Bystander Scenario","volume":"13","author":"Chipuk","year":"2006","journal-title":"Cell Death Differ"},{"key":"B2","doi-asserted-by":"publisher","first-page":"2156","DOI":"10.1093\/bioinformatics\/btr330","article-title":"The Variant Call Format and VCFtools","volume":"27","author":"Danecek","year":"2011","journal-title":"Bioinformatics"},{"key":"B3","doi-asserted-by":"publisher","first-page":"524","DOI":"10.1038\/s41436-020-01010-y","article-title":"Biallelic Variants in HPDL, Encoding 4-hydroxyphenylpyruvate Dioxygenase-like Protein, lead to an Infantile Neurodegenerative Condition","volume":"23","author":"Ghosh","year":"2020","journal-title":"Genet. 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