{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,23]],"date-time":"2026-09-23T16:53:46Z","timestamp":1790182426601,"version":"4.1.0"},"reference-count":28,"publisher":"Wiley","issue":"6","license":[{"start":{"date-parts":[[2022,9,5]],"date-time":"2022-09-05T00:00:00Z","timestamp":1662336000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["JIMD Reports"],"published-print":{"date-parts":[[2022,11]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>In maple syrup urine disease (MSUD), leucine (Leu) accumulation, and its metabolites cause brain toxicity, and at diagnosis rapid plasma Leu reduction is essential. Valine (Val) and isoleucine (Iso) supplements are necessary to promote anabolism and enable prompt reduction of plasma Leu. Val\/Iso supplements are unavailable in Iran, so an alternative source was necessary. An emergency protocol was developed using an unconventional source of Val and Iso to prompt reduction of high plasma Leu levels during an acute metabolic crisis to prevent brain encephalopathy and neurological sequelae. Five children with classical MSUD were referred aged 1\u201325\u2009months, with a prolonged high plasma Leu of more than 1500\u2009\u03bcmol\/L and acute symptoms (irritability, poor feeding, and hypotonia). Initially, breast milk\/regular infant formula was stopped. Val and Iso were given in calculated amounts from a Leu\u2010free formula containing Iso\/Val (Xleu Maxamaid, Nutricia Ltd.) to promote anabolism. It was prescribed for a controlled and limited time with a branched chain amino acid (BCAA) free formula. Frequent amino acid monitoring was conducted. Natural protein was re\u2010added after normalizing plasma Leu. Plasma Leu declined by a median (range) of 1677 (1501\u20131852)\u00a0\u03bcmol\/L within 3\u20134\u2009days of intervention. The median follow\u2010up time was 24\u2009months (range: 14\u201332) and patients showed improvement in motor and cognitive skills after normalizing plasma Leu (75\u2013200\u2009\u03bcmol\/L). Most had improvement in their head circumference (<jats:italic>n<\/jats:italic>\u00a0=\u20094). Due to the unavailability of individual Val\/Iso supplements, a Leu\u2010free formula rapidly lowered plasma Leu concentrations during acute crisis, to prevent cerebral edema and brain damage in MSUD.<\/jats:p>","DOI":"10.1002\/jmd2.12327","type":"journal-article","created":{"date-parts":[[2022,9,5]],"date-time":"2022-09-05T08:09:20Z","timestamp":1662365360000},"page":"555-562","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":4,"title":["Alternative sources of valine and isoleucine for prompt reduction of plasma leucine in maple syrup urine disease patients: A case series"],"prefix":"10.1002","volume":"63","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-0970-3805","authenticated-orcid":false,"given":"Maryam","family":"Ziadlou","sequence":"first","affiliation":[{"name":"Department of Food Science and Technology, Science and Research Branch Islamic Azad University  Tehran Iran"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anita","family":"MacDonald","sequence":"additional","affiliation":[{"name":"Dietetic Department, Birmingham Children's Hospital  Birmingham UK"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2022,9,5]]},"reference":[{"key":"e_1_2_14_2_1","doi-asserted-by":"publisher","DOI":"10.1152\/ajpendo.00193.2003"},{"issue":"4","key":"e_1_2_14_3_1","doi-asserted-by":"crossref","first-page":"903","DOI":"10.1093\/brain\/awp024","article-title":"Dual mechanism of brain injury and novel treatment strategy in maple syrup urine disease","volume":"132","author":"Zinnanti WJ","year":"2009","journal-title":"Brain"},{"key":"e_1_2_14_4_1","doi-asserted-by":"publisher","DOI":"10.1002\/path.1700810209"},{"key":"e_1_2_14_5_1","doi-asserted-by":"publisher","DOI":"10.1203\/01.pdr.0000190571.60385.34"},{"key":"e_1_2_14_6_1","doi-asserted-by":"publisher","DOI":"10.1542\/peds.109.6.999"},{"key":"e_1_2_14_7_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0022-3476(05)81037-6"},{"key":"e_1_2_14_8_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ymgme.2017.09.012"},{"key":"e_1_2_14_9_1","doi-asserted-by":"publisher","DOI":"10.1007\/978-3-319-14621-8"},{"key":"e_1_2_14_10_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ymgme.2014.05.006"},{"key":"e_1_2_14_11_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ymgme.2009.12.007"},{"key":"e_1_2_14_12_1","volume-title":"Nutrition and Diet Therapy in PKU (Phenylketonuria) along with the Low Protein Foods Recipes","author":"Tofighi R","year":"2014"},{"key":"e_1_2_14_13_1","doi-asserted-by":"publisher","DOI":"10.1007\/978-3-030-94510-7_17"},{"key":"e_1_2_14_14_1","doi-asserted-by":"publisher","DOI":"10.3390\/nu2090965"},{"key":"e_1_2_14_15_1","unstructured":"FAO.Food and agricultural organization fats and fatty acids in human nutrition.Report of an Expert Consultation. Geneva Switzerland November 10\u201314 2008."},{"key":"e_1_2_14_16_1","doi-asserted-by":"publisher","DOI":"10.1111\/nure.12071"},{"key":"e_1_2_14_17_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.plipres.2013.10.002"},{"key":"e_1_2_14_18_1","unstructured":"GMDI.MSUD Nutrition Management Guidelines. April 2018;https:\/\/southeastgenetics.org\/ngp\/guidelines.php\/105\/me\/0\/0\/MSUD%20Nutrition%20Guidelines\/Version%201.54\/Monitoring%20and%20Evaluation"},{"key":"e_1_2_14_19_1","doi-asserted-by":"publisher","DOI":"10.1001\/jama.2013.281053"},{"key":"e_1_2_14_20_1","doi-asserted-by":"publisher","DOI":"10.1111\/ced.12876"},{"key":"e_1_2_14_21_1","doi-asserted-by":"publisher","DOI":"10.1007\/s13312-016-0922-0"},{"key":"e_1_2_14_22_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0151-9638(06)70919-X"},{"key":"e_1_2_14_23_1","first-page":"3905658","article-title":"Skin lesions associated with nutritional management of maple syrup urine disease","volume":"2017","author":"Uaariyapanichkul J","year":"2017","journal-title":"Case Rep Dermatol Med"},{"key":"e_1_2_14_24_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ymgmr.2016.10.004"},{"key":"e_1_2_14_25_1","doi-asserted-by":"publisher","DOI":"10.1007\/s10571-013-0002-0"},{"key":"e_1_2_14_26_1","doi-asserted-by":"publisher","DOI":"10.1007\/s11940-003-0039-3"},{"key":"e_1_2_14_27_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ymgme.2020.01.006"},{"key":"e_1_2_14_28_1","doi-asserted-by":"publisher","DOI":"10.1007\/s12687-016-0281-5"},{"key":"e_1_2_14_29_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ymgme.2004.11.010"}],"container-title":["JIMD Reports"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/jmd2.12327","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/full-xml\/10.1002\/jmd2.12327","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/jmd2.12327","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,8,22]],"date-time":"2023-08-22T03:05:39Z","timestamp":1692673539000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1002\/jmd2.12327"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2022,9,5]]},"references-count":28,"journal-issue":{"issue":"6","published-print":{"date-parts":[[2022,11]]}},"alternative-id":["10.1002\/jmd2.12327"],"URL":"https:\/\/doi.org\/10.1002\/jmd2.12327","archive":["Portico"],"relation":{},"ISSN":["2192-8312","2192-8312"],"issn-type":[{"value":"2192-8312","type":"print"},{"value":"2192-8312","type":"electronic"}],"subject":[],"published":{"date-parts":[[2022,9,5]]},"assertion":[{"value":"2022-08-11","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2022-08-20","order":1,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2022-09-05","order":2,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}]}}