{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,11,6]],"date-time":"2025-11-06T11:34:39Z","timestamp":1762428879060,"version":"build-2065373602"},"reference-count":28,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2025,11,6]],"date-time":"2025-11-06T00:00:00Z","timestamp":1762387200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Genet."],"abstract":"<jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>\n                      D-bifunctional protein deficiency (D-BPD) is a rare fatal autosomal recessive peroxisomal disorder caused by biallelic pathogenic mutations in the hydroxysteroid 17-beta dehydrogenase 4 (\n                      <jats:italic>HSD17B4<\/jats:italic>\n                      ) gene; it is characterized by hypotonia, seizures, and facial dysmorphisms during the neonatal period.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Case presentation<\/jats:title>\n                    <jats:p>\n                      In this report, we describe a female neonate from China who was diagnosed with D-BPD. The patient presented with neonatal asphyxia, hypotonia, weak reflexes, and feeding difficulty after birth. Seizures occurred on the fifth day of life and were initially treated with phenobarbital. However, the seizures reoccurred and became more difficult to control because of their increased frequency, duration, and anticonvulsive drug resistance. Whole-genome sequencing (WGS) revealed novel compound heterozygous mutations c.1145G&amp;gt;A(p.Gly382Asp)\/c.1193C&amp;gt;G(p.Ser398*) in exon 13 of the\n                      <jats:italic>HSD17B4<\/jats:italic>\n                      gene, which was confirmed by parental Sanger sequencing. Neither variant has been reported previously. Very-long-chain fatty acid (VLCFA) testing revealed markedly elevated levels of hexacosanoic acid (C26:0), tetracosanoic acid\/docosanoic acid (C24:0\/C22:0), and C26:0\/C22:0. The patient was managed with formula nasogastric feeding and antiepileptic therapy. At 7\u00a0months of age, she demonstrated severe psychomotor retardation, inability to grasp and manipulate objects, no language development, hearing loss, and poor visual response.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>\n                      We described the incidence of D-BPD in a Chinese neonate caused by novel biallelic pathogenic variants in\n                      <jats:italic>HSD17B4<\/jats:italic>\n                      , which expands its mutational spectrum.\n                    <\/jats:p>\n                  <\/jats:sec>","DOI":"10.3389\/fgene.2025.1631767","type":"journal-article","created":{"date-parts":[[2025,11,5]],"date-time":"2025-11-05T22:10:27Z","timestamp":1762380627000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":0,"title":["Case Report: D-bifunctional protein deficiency caused by novel compound heterozygote HSD17B4 variants in a neonate in China"],"prefix":"10.3389","volume":"16","author":[{"given":"Hui","family":"Liu","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Gaojie","family":"Liu","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Lianjun","family":"Gao","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Hui","family":"Wang","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yizhong","family":"Wang","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Hongfang","family":"Ding","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1965","published-online":{"date-parts":[[2025,11,6]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","first-page":"e2519090","DOI":"10.1001\/jamanetworkopen.2025.19090","article-title":"Early-onset neonatal infection and epilepsy in children","volume":"8","author":"Andersen","year":"2025","journal-title":"JAMA Netw. Open"},{"key":"B2","doi-asserted-by":"publisher","first-page":"e357","DOI":"10.3346\/jkms.2020.35.e357","article-title":"First case of peroxisomal D-bifunctional protein deficiency with novel HSD17B4 mutations and progressive neuropathy in Korea","volume":"35","author":"Bae","year":"2020","journal-title":"J. Korean Med. Sci."},{"key":"B3","doi-asserted-by":"publisher","first-page":"354","DOI":"10.1038\/s41372-021-01290-5","article-title":"The association between early-onset sepsis and neonatal encephalopathy","volume":"42","author":"Car","year":"2022","journal-title":"J. Perinatol."},{"key":"B4","doi-asserted-by":"publisher","first-page":"679597","DOI":"10.3389\/fped.2021.679597","article-title":"Two novel HSD17B4 heterozygous mutations in association with D-Bifunctional protein deficiency: a case report and literature review","volume":"9","author":"Chen","year":"2021","journal-title":"Front. Pediatr."},{"key":"B5","doi-asserted-by":"publisher","first-page":"397","DOI":"10.1001\/jamapediatrics.2014.3269","article-title":"Hypoxic-ischemic encephalopathy: a review for the clinician","volume":"169","author":"Douglas-Escobar","year":"2015","journal-title":"JAMA Pediatr."},{"key":"B6","doi-asserted-by":"publisher","first-page":"70","DOI":"10.1016\/j.pediatrneurol.2018.09.001","article-title":"Unusual clinical course and imaging of D-Bifunctional protein deficiency, a rare leukodystrophy","volume":"90","author":"Farkas","year":"2019","journal-title":"Pediatr. Neurol."},{"key":"B7","doi-asserted-by":"publisher","first-page":"92","DOI":"10.1002\/ana.20702","article-title":"Clinical and biochemical spectrum of D-bifunctional protein deficiency","volume":"59","author":"Ferdinandusse","year":"2006","journal-title":"Ann. Neurol."},{"key":"B8","doi-asserted-by":"publisher","first-page":"863","DOI":"10.1136\/jmg.33.10.863","article-title":"Zellweger syndrome and associated phenotypes","volume":"33","author":"FitzPatrick","year":"1996","journal-title":"J. Med. Genet."},{"key":"B9","doi-asserted-by":"publisher","first-page":"63","DOI":"10.1385\/cbb:32:1-3:63","article-title":"Peroxisomal beta-oxidation enzymes","author":"Hashimoto","year":"2000","journal-title":"Cell Biochem. Biophys. 32 Spring"},{"key":"B10","doi-asserted-by":"publisher","first-page":"101137","DOI":"10.1016\/j.ymgmr.2024.101137","article-title":"Ataluren-mediated nonsense variant readthrough in D-bifunctional protein deficiency: a case report","volume":"41","author":"Hsu","year":"2024","journal-title":"Mol. Genet. Metab. Rep."},{"key":"B11","doi-asserted-by":"publisher","first-page":"119","DOI":"10.4103\/aian.AIAN_273_18","article-title":"D-bifunctional protein deficiency: a case report of a Turkish child","volume":"22","author":"Incecik","year":"2019","journal-title":"Ann. Indian Acad. Neurol."},{"key":"B12","doi-asserted-by":"publisher","first-page":"624","DOI":"10.1093\/oxfordjournals.jbchem.a021458","article-title":"Purification and properties of human D-3-hydroxyacyl-CoA dehydratase: medium-chain enoyl-CoA hydratase is D-3-hydroxyacyl-CoA dehydratase","volume":"120","author":"Jiang","year":"1996","journal-title":"J. Biochem."},{"key":"B13","doi-asserted-by":"publisher","first-page":"67","DOI":"10.9734\/ajpr\/2023\/v13i3282","article-title":"D-Bifunctional protein deficiency in a neonate, are we Missing? A case series","volume":"13","author":"Kasula","year":"2023","journal-title":"Asian J. Pediatr. Res."},{"key":"B14","doi-asserted-by":"publisher","first-page":"1163","DOI":"10.1007\/s00234-010-0768-4","article-title":"Neurodegeneration in D-bifunctional protein deficiency: diagnostic clues and natural history using serial magnetic resonance imaging","volume":"52","author":"Khan","year":"2010","journal-title":"Neuroradiology"},{"key":"B15","doi-asserted-by":"publisher","first-page":"100631","DOI":"10.1016\/j.ymgmr.2020.100631","article-title":"Four patients with D-bifunctional protein (DBP) deficiency: expanding the phenotypic spectrum of a highly variable disease","volume":"25","author":"Landau","year":"2020","journal-title":"Mol. Genet. Metab. Rep."},{"key":"B16","doi-asserted-by":"publisher","first-page":"6","DOI":"10.1016\/j.jns.2016.11.009","article-title":"Slowly progressive d-bifunctional protein deficiency with survival to adulthood diagnosed by whole-exome sequencing","volume":"372","author":"Matsukawa","year":"2017","journal-title":"J. Neurol. Sci."},{"key":"B17","doi-asserted-by":"publisher","first-page":"90","DOI":"10.1186\/1750-1172-7-90","article-title":"Specific combination of compound heterozygous mutations in 17\u03b2-hydroxysteroid dehydrogenase type 4 (HSD17B4) defines a new subtype of D-bifunctional protein deficiency","volume":"7","author":"McMillan","year":"2012","journal-title":"Orphanet J. Rare Dis."},{"key":"B18","doi-asserted-by":"publisher","first-page":"e53688","DOI":"10.1371\/journal.pone.0053688","article-title":"On the molecular basis of D-bifunctional protein deficiency type III","volume":"8","author":"Mehtala","year":"2013","journal-title":"PLoS One"},{"key":"B19","doi-asserted-by":"publisher","first-page":"1391","DOI":"10.1038\/s41436-021-01171-4","article-title":"Recommendations for reporting of secondary findings in clinical exome and genome sequencing, 2021 update: a policy statement of the American college of medical genetics and genomics (ACMG)","volume":"23","author":"Miller","year":"2021","journal-title":"Genet. Med."},{"key":"B20","doi-asserted-by":"publisher","first-page":"61","DOI":"10.1016\/s0303-7207(00)00388-9","article-title":"Molecular basis of D-bifunctional protein deficiency","volume":"171","author":"Moller","year":"2001","journal-title":"Mol. Cell Endocrinol."},{"key":"B21","doi-asserted-by":"publisher","first-page":"4924","DOI":"10.3390\/ijms25094924","article-title":"D-Bifunctional protein deficiency Diagnosis-A challenge in low resource settings: case report and review of the literature","volume":"25","author":"Ognean","year":"2024","journal-title":"Int. J. Mol. Sci."},{"key":"B22","doi-asserted-by":"publisher","first-page":"282","DOI":"10.1016\/j.ajhg.2010.07.007","article-title":"Mutations in the DBP-deficiency protein HSD17B4 cause ovarian dysgenesis, hearing loss, and ataxia of perrault syndrome","volume":"87","author":"Pierce","year":"2010","journal-title":"Am. J. Hum. Genet."},{"key":"B23","doi-asserted-by":"publisher","first-page":"1172","DOI":"10.1007\/s10545-005-0149-z","article-title":"Normal very-long-chain fatty acids in peroxisomal D-bifunctional protein deficiency: a diagnostic pitfall","volume":"28","author":"Soorani-Lunsing","year":"2005","journal-title":"J. Inherit. Metab. Dis."},{"key":"B24","doi-asserted-by":"publisher","first-page":"S461","DOI":"10.33549\/physiolres.935214","article-title":"Serum biomarkers of hypoxic-ischemic brain injury","volume":"72","author":"Tefr Faridova","year":"2023","journal-title":"Physiol. Res."},{"key":"B25","doi-asserted-by":"publisher","first-page":"771","DOI":"10.1172\/JCI113956","article-title":"Peroxisomal bifunctional enzyme deficiency","volume":"83","author":"Watkins","year":"1989","journal-title":"J. Clin. Invest"},{"key":"B26","doi-asserted-by":"publisher","first-page":"860","DOI":"10.1007\/s12098-025-05582-y","article-title":"Neonatal onset seizures and hypotonia due to D-Bifunctional protein deficiency","volume":"92","author":"Yahia","year":"2025","journal-title":"Indian J. Pediatr."},{"key":"B27","doi-asserted-by":"publisher","first-page":"2329048X211048613","DOI":"10.1177\/2329048X211048613","article-title":"Novel HSD17B4 variants cause progressive leukodystrophy in childhood: case report and literature review","volume":"8","author":"Yamamoto","year":"2021","journal-title":"Child. Neurol. Open"},{"key":"B28","doi-asserted-by":"publisher","first-page":"1058","DOI":"10.7499\/j.issn.1008-8830.2107158","article-title":"D-bifunctional protein deficiency caused by HSD17B4 gene mutation in a neonate","volume":"23","author":"Yang","year":"2021","journal-title":"Zhongguo Dang Dai Er Ke Za Zhi"}],"container-title":["Frontiers in Genetics"],"original-title":[],"link":[{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fgene.2025.1631767\/full","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,11,6]],"date-time":"2025-11-06T11:29:37Z","timestamp":1762428577000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fgene.2025.1631767\/full"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,11,6]]},"references-count":28,"alternative-id":["10.3389\/fgene.2025.1631767"],"URL":"https:\/\/doi.org\/10.3389\/fgene.2025.1631767","relation":{},"ISSN":["1664-8021"],"issn-type":[{"type":"electronic","value":"1664-8021"}],"subject":[],"published":{"date-parts":[[2025,11,6]]},"article-number":"1631767"}}