{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,8,27]],"date-time":"2025-08-27T09:40:22Z","timestamp":1756287622340,"version":"3.44.0"},"reference-count":11,"publisher":"BMJ","issue":"8","content-domain":{"domain":["bmj.com"],"crossmark-restriction":true},"short-container-title":["BMJ Case Rep"],"accepted":{"date-parts":[[2025,7,5]]},"published-print":{"date-parts":[[2025,8]]},"abstract":"<jats:p>Hawkinsinuria, caused by an autosomal dominant gain-of-function variant of 4-hydroxyphenylpyruvate dioxygenase resulting in accumulation of 2-L-cystein-S-yl-1,4-dihydroxy-cyclohex-5-en-1-yl acetic acid (hawkinsin) and tyrosine, typically presents in the neonatal period. Here we report the case of a female adult patient in her early 20s presenting with childhood developmental delay and dyspraxia. She was initially referred to neurology, where baseline imaging and biochemistry were unremarkable. She was subsequently investigated for metabolic disorders, and it was found that plasma organic acids and amino acids were indicative of hawkinsinuria. Furthermore, her mother, who was asymptomatic, was also diagnosed with hawkinsinuria following family screening. Management was conservative, with regular monitoring of tyrosine and phenylalanine levels. Dietary restriction may be considered if tyrosine is elevated or patients become symptomatic. To our knowledge, this is the first reported case of hawkinsinuria presenting symptomatically in an adult patient and the second case of an asymptomatic adult being diagnosed from genetic testing.<\/jats:p>","DOI":"10.1136\/bcr-2024-264777","type":"journal-article","created":{"date-parts":[[2025,8,12]],"date-time":"2025-08-12T02:30:54Z","timestamp":1754965854000},"page":"e264777","update-policy":"https:\/\/doi.org\/10.1136\/crossmarkpolicy","source":"Crossref","is-referenced-by-count":0,"title":["Challenges in diagnosing hawkinsinuria in adulthood: 2 cases from a single family"],"prefix":"10.1136","volume":"18","author":[{"given":"John","family":"Bassett","sequence":"first","affiliation":[{"name":"Adult Inherited Metabolic Diseases, Salford Care Organisation, Northern Care Alliance NHS Foundation Trust, Salford, UK"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Krithikaalakshmi","family":"Sathiyamoorthy","sequence":"additional","affiliation":[{"name":"Royal Marsden Hospital NHS Trust, London, UK"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Alistair","family":"Horman","sequence":"additional","affiliation":[{"name":"Department of Chemical Pathology, Great Ormond Street Hospital for Children, London, UK"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Georgeta","family":"Taylor","sequence":"additional","affiliation":[{"name":"Department of Neurology, Salford Royal Hospitals NHS Trust, Salford, UK"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Hoi Yee Teresa","family":"Wu","sequence":"additional","affiliation":[{"name":"Willink Biochemical Genetics Laboratory, Manchester University NHS Foundation Trust, Manchester, UK"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Stephen","family":"Dent","sequence":"additional","affiliation":[{"name":"Willink Biochemical Genetics Laboratory, Manchester University NHS Foundation Trust, Manchester, UK"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Reena","family":"Sharma","sequence":"additional","affiliation":[{"name":"Adult Inherited Metabolic Diseases, Salford Care Organisation, Northern Care Alliance NHS Foundation Trust, Salford, UK"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"239","published-online":{"date-parts":[[2025,8,11]]},"reference":[{"key":"2025082702080262000_18.8.e264777.1","doi-asserted-by":"crossref","first-page":"209","DOI":"10.1111\/j.1651-2227.1975.tb03823.x","article-title":"A new form of prolonged transient tyrosinemia presenting with severe metabolic acidosis","volume":"64","author":"Danks","year":"1975","journal-title":"Acta Paediatr"},{"key":"2025082702080262000_18.8.e264777.2","doi-asserted-by":"crossref","DOI":"10.1177\/0300060519863543","article-title":"Hawkinsinuria clinical practice guidelines: a Mexican case report and literature review","volume":"48","author":"Cruz-Camino","year":"2020","journal-title":"J Int Med Res"},{"key":"2025082702080262000_18.8.e264777.3","doi-asserted-by":"crossref","first-page":"379","DOI":"10.1016\/j.ymgme.2007.04.008","article-title":"Manifestation of hawkinsinuria in a patient compound heterozygous for hawkinsinuria and tyrosinemia III","volume":"91","author":"Item","year":"2007","journal-title":"Mol Genet Metab"},{"key":"2025082702080262000_18.8.e264777.4","doi-asserted-by":"crossref","first-page":"280","DOI":"10.1093\/oso\/9780195165647.001.0001","volume-title":"Pediatric nutrition in chronic diseases and developmental disorders: prevention, assessment, and treatment","volume":"3","author":"Ekvall","year":"2005"},{"key":"2025082702080262000_18.8.e264777.5","doi-asserted-by":"crossref","first-page":"563","DOI":"10.1515\/jpem-2019-0498","article-title":"Variant analysis of HPD genes from two families showing elevated tyrosine upon newborn screening by tandem mass spectrometry (MS\/MS)","volume":"33","author":"Zhao","year":"2020","journal-title":"J Pediatr Endocrinol Metab"},{"key":"2025082702080262000_18.8.e264777.6","doi-asserted-by":"publisher","DOI":"10.1056\/NEJM198110083051505"},{"key":"2025082702080262000_18.8.e264777.7","doi-asserted-by":"crossref","first-page":"821","DOI":"10.1007\/s10545-016-9963-8","article-title":"Expanding the phenotype of hawkinsinuria: new insights from response to N-acetyl-L-cysteine","volume":"39","author":"Gomez-Ospina","year":"2016","journal-title":"J Inherit Metab Dis"},{"key":"2025082702080262000_18.8.e264777.8","unstructured":"The genome aggregation database (gnomAD) Cambridge, MA. 2025. 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