{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,5,13]],"date-time":"2025-05-13T14:23:24Z","timestamp":1747146204031,"version":"3.40.5"},"reference-count":20,"publisher":"Wiley","issue":"12","license":[{"start":{"date-parts":[[2022,8,9]],"date-time":"2022-08-09T00:00:00Z","timestamp":1660003200000},"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":[[2022,12]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>Cardio\u2010facio\u2010cutaneous syndrome (CFC) (OMIM 115150) is a congenital disease caused by constitutive activation of the Raf\/MEK\/ERK signaling cascade. Unlike aspects of morphological anomalies, metabolic functions related to the disease have garnered little attention. We present severe neuroglycopenic symptoms due to nonketotic hypoglycemia in two children with CFC (Case 1, a 4\u2010year\u2010old male with c.389A\u2009&gt;\u2009G heterozygous variant in <jats:italic>MAP2K1<\/jats:italic>; Case 2, a 3\u2010year\u2010old male with c.770A\u2009&gt;\u2009G heterozygous variant in <jats:italic>BRAF<\/jats:italic>). Case 1 exhibited a nonketotic hypoglycemic coma and clustered left\u2010hemispheric convulsions despite receiving infusion therapy, leading to severe sequelae with choreoathetosis. Brain magnetic resonance imaging of Case 1 showed T2\u2010elongation with restricted diffusion on the bilateral basal ganglia and thalamus, with the dominance of the right putamen. Case 2 presented a prolonged generalized seizure as an initial clinical symptom but fully recovered. The presence of growth hormone and cortisol deficiency was ruled out in both cases. Blood spots acylcarnitine profiles excluded the co\u2010occurrence of mitochondrial HMG\u2010CoA synthase deficiency and HMG\u2010CoA lyase deficiency. These cases demonstrate the potential vulnerability to nonketotic hypoglycemia, especially during lipid shortages. As children with CFC frequently have difficulties feeding, we suggest great attention should be paid to the potential risk of severe nonketotic hypoglycemia.<\/jats:p>","DOI":"10.1002\/ajmg.a.62926","type":"journal-article","created":{"date-parts":[[2022,8,9]],"date-time":"2022-08-09T12:49:01Z","timestamp":1660049341000},"page":"3505-3509","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["Severe neuroglycopenic symptoms due to nonketotic hypoglycemia in children with cardio\u2010facio\u2010cutaneous syndrome"],"prefix":"10.1002","volume":"188","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-0076-5882","authenticated-orcid":false,"given":"Tadashi","family":"Shiohama","sequence":"first","affiliation":[{"name":"Department of Pediatrics Chiba University Graduate School of Medicine  Chiba Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Katsunori","family":"Fujii","sequence":"additional","affiliation":[{"name":"Department of Pediatrics Chiba University Graduate School of Medicine  Chiba Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4367-6129","authenticated-orcid":false,"given":"Rika","family":"Kosaki","sequence":"additional","affiliation":[{"name":"Division of Medical Genetics National Center for Child Health and Development  Tokyo Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yoshimi","family":"Watanabe","sequence":"additional","affiliation":[{"name":"Division of Child Neurology Chiba Children's Hospital  Chiba Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Tomoko","family":"Uchida","sequence":"additional","affiliation":[{"name":"Department of Pediatrics Chiba University Graduate School of Medicine  Chiba Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Sho","family":"Hagiwara","sequence":"additional","affiliation":[{"name":"Department of Pediatrics Chiba University Graduate School of Medicine  Chiba Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Kaori","family":"Kinoshita","sequence":"additional","affiliation":[{"name":"Department of Pediatrics Kimitsu Chuo Hospital  Chiba Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Katsuo","family":"Sugita","sequence":"additional","affiliation":[{"name":"Research Center for Child Mental Development Chiba University  Chiba Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yoko","family":"Aoki","sequence":"additional","affiliation":[{"name":"Department of Medical Genetics Tohoku University School of Medicine  Sendai Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Naoki","family":"Shimojo","sequence":"additional","affiliation":[{"name":"Department of Pediatrics Chiba University Graduate School of Medicine  Chiba Japan"},{"name":"Center for Preventive Medical Sciences Chiba University  Chiba Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2022,8,9]]},"reference":[{"key":"e_1_2_10_2_1","doi-asserted-by":"publisher","DOI":"10.1002\/ajmg.a.31011"},{"key":"e_1_2_10_3_1","doi-asserted-by":"publisher","DOI":"10.1186\/s13023-021-01797-2"},{"key":"e_1_2_10_4_1","doi-asserted-by":"publisher","DOI":"10.1007\/s10545-014-9704-9"},{"key":"e_1_2_10_5_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jpeds.2017.08.080"},{"key":"e_1_2_10_6_1","doi-asserted-by":"publisher","DOI":"10.1002\/ajmg.a.30189"},{"key":"e_1_2_10_7_1","doi-asserted-by":"publisher","DOI":"10.1016\/0009-8981(83)90371-6"},{"key":"e_1_2_10_8_1","doi-asserted-by":"publisher","DOI":"10.1097\/01.sla.0000118569.10289.ad"},{"key":"e_1_2_10_9_1","doi-asserted-by":"publisher","DOI":"10.1002\/(sici)1520-7560(199911\/12)15:6<412::aid-dmrr72>3.0.co;2-8"},{"key":"e_1_2_10_10_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jpeds.2015.11.076"},{"key":"e_1_2_10_11_1","doi-asserted-by":"publisher","DOI":"10.1111\/1742-6723.13276"},{"key":"e_1_2_10_12_1","doi-asserted-by":"crossref","unstructured":"Monde A. A. Djessou S. P. Camara C. M. Tiahou G. G. Koffi G. Djohan F. Adonis\u2010Koffi L. &Sess Essiagne D. E.(2010).Prevalence of ketotic hypoglycaemia among schoolchildren in the village of Ahou\u00e9 in C\u00f4te\u2010d'Ivoire. 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