{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,17]],"date-time":"2026-08-17T14:26:29Z","timestamp":1786976789918,"version":"build-2736575974"},"reference-count":31,"publisher":"Wiley","issue":"8","license":[{"start":{"date-parts":[[2024,4,3]],"date-time":"2024-04-03T00:00:00Z","timestamp":1712102400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"},{"start":{"date-parts":[[2024,4,3]],"date-time":"2024-04-03T00:00:00Z","timestamp":1712102400000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["American J of Med Genetics Pt A"],"published-print":{"date-parts":[[2024,8]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>\n                    Monoallelic pathogenic\n                    <jats:italic>HMBS<\/jats:italic>\n                    variants are a well\u2010established cause of acute intermittent porphyria (AIP), whereas biallelic pathogenic variants may cause\n                    <jats:italic>HMBS<\/jats:italic>\n                    \u2010related leukoencephalopathy which remains a poorly characterized disorder. We describe an 8\u2010year\u2010old girl with hypotonia, hearing impairment, horizontal nystagmus, bilateral strabismus, impaired visual acuity, and optic nerve atrophy. She had no epilepsy but sleep electroencephalogram showed paroxysmal changes in the right hemisphere with secondary generalizations. Brain magnetic resonance imaging was unremarkable apart from a few small white matter hyperintensities. Exome sequencing (ES) initially prioritized a\n                    <jats:italic>SCN3A<\/jats:italic>\n                    c.3822G&gt;A de novo variant whose sole causative role was eventually questioned as not fully compatible with symptoms. ES reanalysis revealed a homozygous c.674G&gt;A\n                    <jats:italic>HMBS<\/jats:italic>\n                    variant. In the monoallelic form this variant is a known cause of AIP, whereas\n                    <jats:italic>in trans<\/jats:italic>\n                    with another\n                    <jats:italic>HMBS<\/jats:italic>\n                    pathogenic variant it was associated with the\n                    <jats:italic>HMBS<\/jats:italic>\n                    \u2010related leukoencephalopathy in four individuals. Despite lack of signs\/symptoms of porphyria, literature analysis suggested that\n                    <jats:italic>HMBS<\/jats:italic>\n                    c.674G&gt;A likely contributed to the disease either as the sole cause or together with\n                    <jats:italic>SCN3A<\/jats:italic>\n                    c.3822G&gt;A as a part of blended phenotype. Our report adds to the relatively small number of described cases of\n                    <jats:italic>HMBS<\/jats:italic>\n                    \u2010related leukoencephalopathy and emphasizes that autosomal recessive form of\n                    <jats:italic>HMBS<\/jats:italic>\n                    disease can be present in the absence of porphyria symptoms.\n                  <\/jats:p>","DOI":"10.1002\/ajmg.a.63617","type":"journal-article","created":{"date-parts":[[2024,4,3]],"date-time":"2024-04-03T09:39:12Z","timestamp":1712137152000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":2,"title":["Neurodevelopmental disorder in a patient with\n                    <scp>\n                      <i>HMBS<\/i>\n                    <\/scp>\n                    and\n                    <scp>\n                      <i>SCN3A<\/i>\n                    <\/scp>\n                    variants\u2014A possibly blended phenotype further delineating autosomal recessive\n                    <scp>\n                      <i>HMBS<\/i>\n                    <\/scp>\n                    related disease"],"prefix":"10.1002","volume":"194","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-5738-8526","authenticated-orcid":false,"given":"K\u0142aniewska","family":"M","sequence":"first","affiliation":[{"name":"Department of Family and Pediatric Nursing Wroclaw Medical University  Wroclaw Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rydzanicz","family":"M","sequence":"additional","affiliation":[{"name":"Department of Medical Genetics Medical University of Warsaw  Warsaw Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bladowska","family":"J","sequence":"additional","affiliation":[{"name":"Department of Radiology, Wroclaw 4th Military Clinical Hospital, Faculty of Medicine Wroclaw University of Science and Technology  Wroclaw Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Borys \u2010 Iwanicka","family":"A","sequence":"additional","affiliation":[{"name":"Department of Paediatrics, Gastroenterology and Nutrition Wroclaw Medical University  Wroclaw Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Iwanicka \u2010 Pronicka","family":"K","sequence":"additional","affiliation":[{"name":"Department of Medical Genetics The Children's Memorial Health Institute  Warsaw Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wasilewski","family":"R","sequence":"additional","affiliation":[{"name":"Department of Disorders of Hemostasis and Internal Medicine Institute of Hematology and Transfusion Medicine  Warsaw Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Odnoczko","family":"E","sequence":"additional","affiliation":[{"name":"Laboratory of Genetics in Hemostasis and Porphyria, Department of Hemostasis and Metabolic Disorders Institute of Hematology and Transfusion Medicine  Warsaw Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zubkiewicz\u2010Kucharska","family":"A","sequence":"additional","affiliation":[{"name":"Department of Pediatrics, Endocrinology, Diabetology and Metabolic Diseases Medical University of Wroclaw  Wroclaw Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Smigiel","family":"R","sequence":"additional","affiliation":[{"name":"Department of Pediatrics, Endocrinology, Diabetology and Metabolic Diseases Medical University of Wroclaw  Wroclaw Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6286-5526","authenticated-orcid":false,"given":"Ploski","family":"R","sequence":"additional","affiliation":[{"name":"Department of Medical Genetics Medical University of Warsaw  Warsaw Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2024,4,3]]},"reference":[{"key":"e_1_2_9_2_1","doi-asserted-by":"publisher","DOI":"10.1101\/gr.183483.114"},{"key":"e_1_2_9_3_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.biopsych.2017.01.009"},{"key":"e_1_2_9_4_1","doi-asserted-by":"publisher","DOI":"10.1111\/epi.16438"},{"key":"e_1_2_9_5_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.gene.2013.09.073"},{"key":"e_1_2_9_6_1","doi-asserted-by":"publisher","DOI":"10.1002\/humu.23067"},{"key":"e_1_2_9_7_1","doi-asserted-by":"publisher","DOI":"10.1172\/JCI117543"},{"key":"e_1_2_9_8_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.seizure.2018.06.012"},{"key":"e_1_2_9_9_1","first-page":"731","article-title":"A child with a special form of porphyria","volume":"32","author":"Villeneuve V. H.","year":"1964","journal-title":"Maandschrift Voor Kindergeneeskunde"},{"key":"e_1_2_9_10_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ajhg.2013.08.006"},{"key":"e_1_2_9_11_1","doi-asserted-by":"publisher","DOI":"10.1034\/j.1399-0004.2002.620406.x"},{"key":"e_1_2_9_12_1","first-page":"1993","volume-title":"GeneReviews\u00ae [Internet]","author":"Helbig K. L.","year":"2021"},{"key":"e_1_2_9_13_1","doi-asserted-by":"publisher","DOI":"10.1023\/B:BOLI.0000016613.75677.05"},{"key":"e_1_2_9_14_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.braindev.2019.09.004"},{"key":"e_1_2_9_15_1","doi-asserted-by":"publisher","DOI":"10.1093\/brain\/awab321"},{"key":"e_1_2_9_16_1","doi-asserted-by":"publisher","DOI":"10.1212\/WNL.0000000000003129"},{"key":"e_1_2_9_17_1","doi-asserted-by":"publisher","DOI":"10.1093\/bioinformatics\/bty897"},{"key":"e_1_2_9_18_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.nbd.2017.02.006"},{"key":"e_1_2_9_19_1","doi-asserted-by":"publisher","DOI":"10.1093\/hmg\/ddy030"},{"key":"e_1_2_9_20_1","doi-asserted-by":"publisher","DOI":"10.1007\/BF00207051"},{"key":"e_1_2_9_21_1","doi-asserted-by":"publisher","DOI":"10.1186\/1744-8069-2-33"},{"key":"e_1_2_9_22_1","doi-asserted-by":"publisher","DOI":"10.1186\/s12888-018-1822-8"},{"key":"e_1_2_9_23_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0140-6736(09)61925-5"},{"key":"e_1_2_9_24_1","doi-asserted-by":"publisher","DOI":"10.1093\/nar\/14.15.5955"},{"key":"e_1_2_9_25_1","doi-asserted-by":"publisher","DOI":"10.1038\/gim.2015.30"},{"key":"e_1_2_9_26_1","doi-asserted-by":"publisher","DOI":"10.3390\/jcm9072220"},{"key":"e_1_2_9_27_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.neuron.2018.07.052"},{"key":"e_1_2_9_28_1","doi-asserted-by":"publisher","DOI":"10.1001\/archneur.acit1.11.1764"},{"key":"e_1_2_9_29_1","doi-asserted-by":"publisher","DOI":"10.1002\/ajmg.a.62377"},{"key":"e_1_2_9_30_1","doi-asserted-by":"publisher","DOI":"10.1212\/NXG.0000000000000170"},{"key":"e_1_2_9_31_1","doi-asserted-by":"publisher","DOI":"10.1126\/science.1254806"},{"key":"e_1_2_9_32_1","doi-asserted-by":"publisher","DOI":"10.1002\/ana.25809"}],"container-title":["American Journal of Medical Genetics Part A"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/ajmg.a.63617","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/full-xml\/10.1002\/ajmg.a.63617","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/ajmg.a.63617","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,2,18]],"date-time":"2026-02-18T07:29:11Z","timestamp":1771399751000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1002\/ajmg.a.63617"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2024,4,3]]},"references-count":31,"journal-issue":{"issue":"8","published-print":{"date-parts":[[2024,8]]}},"alternative-id":["10.1002\/ajmg.a.63617"],"URL":"https:\/\/doi.org\/10.1002\/ajmg.a.63617","archive":["Portico"],"relation":{},"ISSN":["1552-4825","1552-4833"],"issn-type":[{"value":"1552-4825","type":"print"},{"value":"1552-4833","type":"electronic"}],"subject":[],"published":{"date-parts":[[2024,4,3]]},"assertion":[{"value":"2023-03-28","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2024-03-22","order":2,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2024-04-03","order":3,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}],"article-number":"e63617"}}