{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,25]],"date-time":"2026-10-25T11:40:30Z","timestamp":1792928430380,"version":"4.5.0"},"reference-count":31,"publisher":"Wiley","issue":"1","license":[{"start":{"date-parts":[[2023,10,10]],"date-time":"2023-10-10T00:00:00Z","timestamp":1696896000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Molec Gen &amp;amp; Gen Med"],"published-print":{"date-parts":[[2024,1]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:sec><jats:title>Background<\/jats:title><jats:p>Hereditary tyrosinemia type III (HT III) is an extremely rare form of tyrosinemia, characterized by autosomal recessive inheritance and biallelic mutations in the <jats:italic>HPD<\/jats:italic> gene. The clinical presentation of HT III is variable and poorly understood, with symptoms ranging from developmental delay and intellectual impairment to seizures and intermittent ataxia. This study aimed to provide further insights into the clinical and genetic characteristics of HT III.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>A 3\u2010year\u2010old girl, identified through newborn screening, was diagnosed with HT III using targeted next\u2010generation sequencing. A comprehensive literature review was conducted, and the clinical, biochemical, and genetic findings of previously reported HT III patients were summarized and analyzed.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>The genetic analysis of the proband revealed compound heterozygous mutations in the <jats:italic>HPD<\/jats:italic> gene such as c.731C&gt;T (p.A244V) and c.656C&gt;T (p.T219M). Notably, the <jats:italic>HPD<\/jats:italic> p.A244V mutation had not been previously documented in public databases or the scientific literature. Bioinformatics analysis classified both variants as pathogenic variants. The patient exhibited persistent tyrosinemia, elevated levels of related metabolite derivatives, confirming the diagnosis of HT III. The review of previously published cases contributed to a better understanding of the clinical and genetic characteristics associated with HT III.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusion<\/jats:title><jats:p>Early diagnosis and prompt treatment in infancy are crucial for managing HT III effectively. Dietary therapy, particularly during childhood, plays a significant role in disease management. The findings from this study enhance our understanding of the genotype\u2013phenotype associations in HT III and emphasize the importance of early intervention for improved patient outcomes.<\/jats:p><\/jats:sec>","DOI":"10.1002\/mgg3.2298","type":"journal-article","created":{"date-parts":[[2023,10,12]],"date-time":"2023-10-12T04:43:16Z","timestamp":1697085796000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":3,"title":["Novel <scp>HPD<\/scp> mutation p.<scp>A244V<\/scp> compound with p.<scp>T219M<\/scp> causing tyrosinemia type <scp>III<\/scp> in a Chinese girl and review of the genotype\u2013phenotype spectrum"],"prefix":"10.1002","volume":"12","author":[{"given":"Dong","family":"Han","sequence":"first","affiliation":[{"name":"Medical Genetic Center, Changzhi Maternal and Child Health Care Hospital  Changzhi Shanxi China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lihong","family":"Wang","sequence":"additional","affiliation":[{"name":"Department of Pediatrics Changzhi Maternal and Child Health Care Hospital  Changzhi Shanxi China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chen","family":"Zhao","sequence":"additional","affiliation":[{"name":"Department of Pediatrics Changzhi Maternal and Child Health Care Hospital  Changzhi Shanxi China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Juan","family":"Li","sequence":"additional","affiliation":[{"name":"Medical Genetic Center, Changzhi Maternal and Child Health Care Hospital  Changzhi Shanxi China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chenggang","family":"Huang","sequence":"additional","affiliation":[{"name":"Zhejiang Biosan Biochemical Technologies Co., Ltd.  Hangzhou Zhejiang China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wenxia","family":"Song","sequence":"additional","affiliation":[{"name":"Obstetrics Department Changzhi Maternal and Child Health Care Hospital  Changzhi Shanxi China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Haiwei","family":"Wang","sequence":"additional","affiliation":[{"name":"Science and Education Division Changzhi Maternal and Child Health Care Hospital  Changzhi Shanxi China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiaoze","family":"Li","sequence":"additional","affiliation":[{"name":"Medical Genetic Center, Changzhi Maternal and Child Health Care Hospital  Changzhi Shanxi China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8787-9622","authenticated-orcid":false,"given":"Yilun","family":"Tao","sequence":"additional","affiliation":[{"name":"Medical Genetic Center, Changzhi Maternal and Child Health Care Hospital  Changzhi Shanxi China"},{"name":"Precision Medicine Research Division Changzhi Maternal and Child Health Care Hospital  Changzhi Shanxi China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2023,10,10]]},"reference":[{"key":"e_1_2_12_2_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pgen.1008409"},{"key":"e_1_2_12_3_1","doi-asserted-by":"publisher","DOI":"10.1093\/nar\/gki375"},{"key":"e_1_2_12_4_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1651\u20102227.1997.tb15192.x"},{"key":"e_1_2_12_5_1","doi-asserted-by":"publisher","DOI":"10.1023\/a:1013936107064"},{"key":"e_1_2_12_6_1","doi-asserted-by":"publisher","DOI":"10.1007\/BF02179153"},{"key":"e_1_2_12_7_1","volume-title":"Clinical genetic and metabolic diseases","author":"Gu X.","year":"2015"},{"key":"e_1_2_12_8_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0021-9258(18)64891-4"},{"key":"e_1_2_12_9_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ymgme.2012.09.002"},{"key":"e_1_2_12_10_1","doi-asserted-by":"publisher","DOI":"10.1016\/B978-0-12-816926-1.00024-9"},{"key":"e_1_2_12_11_1","doi-asserted-by":"publisher","DOI":"10.1159\/000519256"},{"key":"e_1_2_12_12_1","doi-asserted-by":"publisher","DOI":"10.1093\/bioinformatics\/bty897"},{"key":"e_1_2_12_13_1","doi-asserted-by":"publisher","DOI":"10.4103\/2277\u20109175.223740"},{"key":"e_1_2_12_14_1","doi-asserted-by":"publisher","DOI":"10.1107\/S2059798320006002"},{"key":"e_1_2_12_15_1","doi-asserted-by":"publisher","DOI":"10.1093\/bioinformatics\/btm076"},{"issue":"1","key":"e_1_2_12_16_1","article-title":"A new case of tyrosinemia type III detected by neonatal screening","volume":"19","author":"Praece M. 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