{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,4]],"date-time":"2026-08-04T09:46:37Z","timestamp":1785836797751,"version":"3.56.0"},"reference-count":29,"publisher":"Wiley","issue":"9","license":[{"start":{"date-parts":[[2026,4,12]],"date-time":"2026-04-12T00:00:00Z","timestamp":1775952000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"},{"start":{"date-parts":[[2026,4,12]],"date-time":"2026-04-12T00:00:00Z","timestamp":1775952000000},"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":[[2026,9]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:p>\n                    Fumarase deficiency (FMRD) is a rare autosomal recessive disorder caused by fumarate hydratase (FH) deficiency, with variable presentation from severe early\u2010onset encephalopathy to mild cognitive impairment. Heterozygous carriers of some variants are predisposed to hereditary leiomyomatosis and renal cell carcinoma (HLRCC). We retrospectively reviewed clinical, biochemical, and molecular data from patients with confirmed or suspected FMRD across three metabolic centers in Northern England. Ten patients (seven females, three males) from seven families were identified, with a median diagnostic age of 5\u2009years (range: 1\u2009day\u201316\u2009years). All had developmental delay and learning difficulties of varying severity. Elevated urinary fumarate was found in 7\/10 patients but was inconsistent on repeat analysis. Five patients had neutropenia, and four had abnormal neuroimaging findings. Biallelic\n                    <jats:italic>FH<\/jats:italic>\n                    variants were identified in nine patients, comprising five variants: four missense and one in\u2010frame duplication. The c.410C&gt;T variant accounted for 44% of mutant alleles, and three patients were homozygous for c.1431_1433dupAAA p.(Lys477dup). Renal lesions were detected in two heterozygous fathers. Elevated urinary fumarate was not a consistent feature in some patients. The c.1431_1433dupAAA variant was identified in the homozygous state in patients with mild intellectual disability and features overlapping with FMRD. Our findings suggest that all variants identified in FMRD patients require independent clinical evaluation for HLRCC association.\n                  <\/jats:p>","DOI":"10.1002\/ajmg.a.70160","type":"journal-article","created":{"date-parts":[[2026,4,13]],"date-time":"2026-04-13T03:44:33Z","timestamp":1776051873000},"page":"2000-2009","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["A Diagnostic Conundrum in Fumarase Deficiency: Expanding the Clinical and Genetic Spectrum in a Cohort of Pediatric and Adult Patients"],"prefix":"10.1002","volume":"200","author":[{"ORCID":"https:\/\/orcid.org\/0009-0007-6408-9699","authenticated-orcid":false,"given":"Siew Li","family":"Ting","sequence":"first","affiliation":[{"name":"Willink Metabolic Unit, Genomic Medicine, St Mary's Hospital, Manchester University NHS Foundation Trust  Manchester UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"John","family":"Bassett","sequence":"additional","affiliation":[{"name":"Adult Inherited Metabolic Diseases, Salford Royal Hospital, Northern Care Alliance NHS Foundation Trust  Salford UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jonathan","family":"Meyer","sequence":"additional","affiliation":[{"name":"Adult Inherited Metabolic Diseases, Salford Royal Hospital, Northern Care Alliance NHS Foundation Trust  Salford UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mark","family":"Anderson","sequence":"additional","affiliation":[{"name":"Great North Children's Hospital, Newcastle Upon Tyne Hospitals NHS Foundation Trust  Newcastle Upon Tyne UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ann","family":"Bowron","sequence":"additional","affiliation":[{"name":"Department of Blood Sciences Newcastle Upon Tyne Hospitals NHS Foundation Trust  Newcastle Upon Tyne UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Astrid","family":"Weber","sequence":"additional","affiliation":[{"name":"Liverpool Centre for Genomic Medicine, Liverpool Women's Hospital, Liverpool Women's NHS Foundation Trust  Liverpool UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Teresa H. 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