{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,11,25]],"date-time":"2025-11-25T20:42:16Z","timestamp":1764103336565,"version":"3.40.5"},"reference-count":18,"publisher":"Wiley","issue":"2","license":[{"start":{"date-parts":[[2022,11,11]],"date-time":"2022-11-11T00:00:00Z","timestamp":1668124800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["American J of Med Genetics Pt A"],"published-print":{"date-parts":[[2023,2]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>5\u2010Amino\u20104\u2010imidazolecarboxamide\u2010ribosiduria (AICA\u2010ribosiduria) is an extremely rare inborn error of purine biosynthesis metabolism caused by pathogenic variants in ATIC gene that encodes a protein catalyzing the last steps of the de novo purine biosynthesis. To date, only six cases have been reported presenting a severe phenotype characterized by coarse facies and variable dysmorphic features, intrauterine and postnatal growth retardation, severe and early neurodevelopment delay, profound congenital visual deficit, scoliosis and, less frequently, epilepsy, aortic coarctation, chronic hepatic cytolysis, nephrocalcinosis and mild genitalia malformation. In this article, we report two new cases of AICA\u2010ribosiduria carrying new pathogenic variants in <jats:italic>ATIC<\/jats:italic> (c.421C&gt;T;p.Arg141Ter and c.1753A&gt;G p.Thr585Ala) associated to a milder phenotype compared to previously reported patients. Particularly, the children showed few dysmorphic features (bulging forehead, depressed nasal bridge, and flat nasal tip), postnatal growth impairment, psychomotor delay since the second year of life, reduction of visual acuity (from mild impairment to low vision from the age of 5\u2009years and to partial blindness from the age of 7\u2009years) and mild hepatic dysfunctions. Scoliosis as well as epilepsy, renal involvement, or genitalia malformation were not detected. According to literature data, we found an abnormal accumulation of intermediates of de novo purine biosynthesis in the urine of both siblings. This report expands the spectrum of phenotypic severity associated to ATIC biallelic pathogenic variants and prompts the need to investigate ultra\u2010rare causes of metabolic disorders such as AICA\u2010ribosiduria in subjects with early neurological and sensory involvement of uncertain etiology.<\/jats:p>","DOI":"10.1002\/ajmg.a.63036","type":"journal-article","created":{"date-parts":[[2022,11,11]],"date-time":"2022-11-11T12:15:12Z","timestamp":1668168912000},"page":"575-581","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":4,"title":["Expanding the spectrum of clinical severity of <scp>AICA<\/scp>\u2010ribosiduria: Report of two siblings with mild phenotype caused by a novel pathogenic variant in <scp>ATIC<\/scp> gene"],"prefix":"10.1002","volume":"191","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-3347-7548","authenticated-orcid":false,"given":"Jessica","family":"Galli","sequence":"first","affiliation":[{"name":"Department of Clinical and Experimental Sciences University of Brescia  Brescia Italy"},{"name":"Unit of Child Neurology and Psychiatry ASST Spedali Civili of Brescia  Brescia Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Enza Maria","family":"Valente","sequence":"additional","affiliation":[{"name":"Department of Molecular Medicine University of Pavia and Neurogenetics Research Center, IRCCS Mondino Foundation  Pavia Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Joseph","family":"Dewulf","sequence":"additional","affiliation":[{"name":"Laboratoire des Maladies M\u00e9taboliques H\u00e9r\u00e9ditaires\/Biochimie G\u00e9n\u00e9tique et Centre de D\u00e9pistage N\u00e9onatal Cliniques Universitaires Saint\u2010Luc  Brussels Belgium"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Alessandra","family":"Franzoni","sequence":"additional","affiliation":[{"name":"Department of Neurological and Vision Sciences ASST Spedali Civili of Brescia  Brescia Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Sandrine","family":"Marie","sequence":"additional","affiliation":[{"name":"Laboratoire des Maladies M\u00e9taboliques H\u00e9r\u00e9ditaires\/Biochimie G\u00e9n\u00e9tique et Centre de D\u00e9pistage N\u00e9onatal Cliniques Universitaires Saint\u2010Luc  Brussels Belgium"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Massimo","family":"Plumari","sequence":"additional","affiliation":[{"name":"Neurogenetics Research Center, IRCCS Mondino Foundation  Pavia Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Federica","family":"Zanetti","sequence":"additional","affiliation":[{"name":"Department of Clinical and Experimental Sciences University of Brescia  Brescia Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Elisa","family":"Fazzi","sequence":"additional","affiliation":[{"name":"Department of Clinical and Experimental Sciences University of Brescia  Brescia Italy"},{"name":"Unit of Child Neurology and Psychiatry ASST Spedali Civili of Brescia  Brescia Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2022,11,11]]},"reference":[{"key":"e_1_2_8_2_1","doi-asserted-by":"publisher","DOI":"10.1093\/hmg\/ddr591"},{"key":"e_1_2_8_3_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00018-007-6497-0"},{"key":"e_1_2_8_4_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ymgme.2021.12.016"},{"key":"e_1_2_8_5_1","doi-asserted-by":"publisher","DOI":"10.1111\/dmcn.14865"},{"key":"e_1_2_8_6_1","doi-asserted-by":"publisher","DOI":"10.3389\/fnhum.2022.750464"},{"key":"e_1_2_8_7_1","doi-asserted-by":"publisher","DOI":"10.1055\/s-0041-1732430"},{"volume-title":"Griffiths mental development scales (revised)","year":"1996","author":"Griffiths R.","key":"e_1_2_8_8_1"},{"key":"e_1_2_8_9_1","doi-asserted-by":"publisher","DOI":"10.1096\/fasebj.9.7.7737463"},{"key":"e_1_2_8_10_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.braindev.2022.05.004"},{"key":"e_1_2_8_11_1","doi-asserted-by":"publisher","DOI":"10.1001\/jamanetworkopen.2021.14155"},{"key":"e_1_2_8_12_1","doi-asserted-by":"publisher","DOI":"10.1086\/421475"},{"key":"e_1_2_8_13_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ymgmr.2020.100642"},{"key":"e_1_2_8_14_1","doi-asserted-by":"publisher","DOI":"10.2174\/156802611795347645"},{"key":"e_1_2_8_15_1","doi-asserted-by":"publisher","DOI":"10.1002\/jimd.12274"},{"volume-title":"Vineland adaptive behavior scales\u2010II","year":"2016","author":"Sparrow S. 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