{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,10,10]],"date-time":"2025-10-10T01:04:24Z","timestamp":1760058264330,"version":"build-2065373602"},"reference-count":21,"publisher":"MDPI AG","issue":"7","license":[{"start":{"date-parts":[[2025,3,27]],"date-time":"2025-03-27T00:00:00Z","timestamp":1743033600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"ASPIRE","award":["VRI-20-10"],"award-info":[{"award-number":["VRI-20-10"]}]},{"name":"Province of British Columbia, LifeLabs, and Genome BC for the Leading Edge Endowment Funds","award":["VRI-20-10"],"award-info":[{"award-number":["VRI-20-10"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Sepiapterin Reductase Deficiency (SRD) is a rare inherited neurometabolic disorder caused by variants in the SPR gene, which may lead to developmental delays, psychomotor retardation, and cognitive impairments. Two consanguineous North African and Middle Eastern families are reported with multiple affected individuals presenting with developmental delay, ataxia, hypotonia, fatigue, and ptosis, or parkinsonism and cognitive impairment. Exome sequencing revealed a novel homozygous SPR c.560A&gt;G (p.Glu187Gly) mutation that segregates with disease. According to molecular dynamics analysis, the substitution is predicted to compromise structural integrity, likely affecting ligand binding and catalytic activity. Elevated cerebrospinal fluid sepiapterin and biopterin levels, along with low neurotransmitter levels, were concordant with a genetic diagnosis of SRD and the reclassification of this variant as pathogenic. SRD patients manifest a broad constellation of symptoms, albeit well-managed using low-dose L-dopa\/carbidopa. This study highlights the value of genetic testing in expediting early diagnosis and intervention to mitigate the onset of this disorder.<\/jats:p>","DOI":"10.3390\/ijms26073056","type":"journal-article","created":{"date-parts":[[2025,3,28]],"date-time":"2025-03-28T04:11:40Z","timestamp":1743135100000},"page":"3056","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Clinical Features of Families with a Novel Pathogenic Mutation in Sepiapterin Reductase"],"prefix":"10.3390","volume":"26","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-0110-2351","authenticated-orcid":false,"given":"Feda E.","family":"Mohamed","sequence":"first","affiliation":[{"name":"Department of Genetics and Genomics, College of Medicine and Health Sciences, United Arab Emirates University, Al Ain 15551, United Arab Emirates"},{"name":"ASPIRE Precision Medicine Research Institute Abu Dhabi, United Arab Emirates University, Abu Dhabi 15551, United Arab Emirates"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9307-3644","authenticated-orcid":false,"given":"Lara","family":"Alzyoud","sequence":"additional","affiliation":[{"name":"College of Pharmacy, Al Ain University, Abu Dhabi 64141, United Arab Emirates"},{"name":"AAU Health and Biomedical Research Center, Al Ain University, Abu Dhabi 64141, United Arab Emirates"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2240-8037","authenticated-orcid":false,"given":"Mohammad A.","family":"Ghattas","sequence":"additional","affiliation":[{"name":"College of Pharmacy, Al Ain University, Abu Dhabi 64141, United Arab Emirates"},{"name":"AAU Health and Biomedical Research Center, Al Ain University, Abu Dhabi 64141, United Arab Emirates"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Mohammed","family":"Tabouni","sequence":"additional","affiliation":[{"name":"Department of Genetics and Genomics, College of Medicine and Health Sciences, United Arab Emirates University, Al Ain 15551, United Arab Emirates"},{"name":"ASPIRE Precision Medicine Research Institute Abu Dhabi, United Arab Emirates University, Abu Dhabi 15551, United Arab Emirates"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0009-0004-9594-3673","authenticated-orcid":false,"given":"Andr\u00e9","family":"Fienemann","sequence":"additional","affiliation":[{"name":"Institute of Neurogenetics, University of L\u00fcbeck, 23538 L\u00fcbeck, Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Joanne","family":"Trinh","sequence":"additional","affiliation":[{"name":"Institute of Neurogenetics, University of L\u00fcbeck, 23538 L\u00fcbeck, Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ibrahim","family":"Baydoun","sequence":"additional","affiliation":[{"name":"Department of Genetics and Genomics, College of Medicine and Health Sciences, United Arab Emirates University, Al Ain 15551, United Arab Emirates"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2687-6476","authenticated-orcid":false,"given":"Praseetha","family":"Kizhakkedath","sequence":"additional","affiliation":[{"name":"Department of Genetics and Genomics, College of Medicine and Health Sciences, United Arab Emirates University, Al Ain 15551, United Arab Emirates"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Hiba","family":"Alblooshi","sequence":"additional","affiliation":[{"name":"Department of Genetics and Genomics, College of Medicine and Health Sciences, United Arab Emirates University, Al Ain 15551, United Arab Emirates"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Qudsia","family":"Shaukat","sequence":"additional","affiliation":[{"name":"Department of Pediatrics, Tawam Hospital, Al Ain 15258, United Arab Emirates"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Rim","family":"Amouri","sequence":"additional","affiliation":[{"name":"Neurology\u2019s Department, Mongi Ben Hmida National Institute of Neurology, Tunis 1007, Tunisia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1159-5321","authenticated-orcid":false,"given":"Matthew J.","family":"Farrer","sequence":"additional","affiliation":[{"name":"Department of Neurology, University of Florida, Gainesville, FL 32611, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Samia Ben","family":"Sassi","sequence":"additional","affiliation":[{"name":"Neurology\u2019s Department, Mongi Ben Hmida National Institute of Neurology, Tunis 1007, Tunisia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Fatma","family":"Al-Jasmi","sequence":"additional","affiliation":[{"name":"Department of Genetics and Genomics, College of Medicine and Health Sciences, United Arab Emirates University, Al Ain 15551, United Arab Emirates"},{"name":"ASPIRE Precision Medicine Research Institute Abu Dhabi, United Arab Emirates University, Abu Dhabi 15551, United Arab Emirates"},{"name":"Department of Pediatrics, Tawam Hospital, Al Ain 15258, United Arab Emirates"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2025,3,27]]},"reference":[{"key":"ref_1","unstructured":"Adam, M.P., Feldman, J., Mirzaa, G.M., Pagon, R.A., Wallace, S.E., Bean, L.J., Gripp, K.W., and Amemiya, A. 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