{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,5,13]],"date-time":"2025-05-13T15:21:53Z","timestamp":1747149713641,"version":"3.40.5"},"reference-count":17,"publisher":"Wiley","issue":"1","license":[{"start":{"date-parts":[[2021,5,5]],"date-time":"2021-05-05T00:00:00Z","timestamp":1620172800000},"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":[[2021,9]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>Tetrahydrobiopterin (BH<jats:sub>4<\/jats:sub>) is a cofactor that participates in the biogenesis reactions of a variety of biomolecules, including <jats:sc>l<\/jats:sc>\u2010tyrosine, <jats:sc>l<\/jats:sc>\u20103,4\u2010dihydroxyphenylalanine, 5\u2010hydroxytryptophan, nitric oxide, and glycerol. Dihydropteridine reductase (DHPR, EC 1.5.1.34) is an enzyme involved in the BH<jats:sub>4<\/jats:sub> regeneration. DHPR deficiency (DHPRD) is an autosomal recessive disorder, leading to severe and progressive neurological manifestations, which cannot be exclusively controlled by <jats:sc>l<\/jats:sc>\u2010phenylalanine (<jats:sc>l<\/jats:sc>\u2010Phe) restricted diet. In fact, the supplementation of neurotransmitter precursors is more decisive in the disease management, and the administration of sapropterin dihydrochloride may also provide positive effects. From the best of our knowledge, there is limited information regarding DHPRD in the past 5\u2009years in the literature. Here, we describe the medical journey of the first patient to have DHPRD confirmed by molecular diagnostic methods in Brazil. The patient presented with two pathogenic variants of the quinoid dihydropteridine reductase (<jats:italic>QDPR<\/jats:italic>) gene\u2014which codes for the DHPR protein, one containing the in <jats:italic>trans<\/jats:italic> missense mutation c.515C&gt;T (pPro172Leu) in exon 5 and the other containing the same type of mutation in the exon 7 (c.635T&gt;C [p.Phe212Ser]). The authors discuss their experience with sapropterin dihydrochloride for the treatment of DHPRD in this case report.<\/jats:p>","DOI":"10.1002\/jmd2.12224","type":"journal-article","created":{"date-parts":[[2021,5,6]],"date-time":"2021-05-06T16:51:32Z","timestamp":1620319892000},"page":"19-24","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["Sapropterin dihydrochloride therapy in dihydropteridine reductase deficiency: Insight from the first case with molecular diagnosis in Brazil"],"prefix":"10.1002","volume":"61","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-2296-6098","authenticated-orcid":false,"given":"Charles Marques","family":"Louren\u00e7o","sequence":"first","affiliation":[{"name":"Centro Universit\u00e1rio Est\u00e1cio de Ribeir\u00e3o Preto  S\u00e3o Paulo Brazil"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Janaina","family":"Dovidio","sequence":"additional","affiliation":[{"name":"Centro Universit\u00e1rio Est\u00e1cio de Ribeir\u00e3o Preto  S\u00e3o Paulo Brazil"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Isabela F.","family":"Lopes","sequence":"additional","affiliation":[{"name":"Centro Universit\u00e1rio Est\u00e1cio de Ribeir\u00e3o Preto  S\u00e3o Paulo Brazil"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"La\u00eds C.","family":"Silva","sequence":"additional","affiliation":[{"name":"Centro Universit\u00e1rio Est\u00e1cio de Ribeir\u00e3o Preto  S\u00e3o Paulo Brazil"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Marcela","family":"Almeida","sequence":"additional","affiliation":[{"name":"Centro Universit\u00e1rio Est\u00e1cio de Ribeir\u00e3o Preto  S\u00e3o Paulo Brazil"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Laura","family":"Vagnini","sequence":"additional","affiliation":[{"name":"Centro Paulista de Diagn\u00f3stico e Pesquisa em Gen\u00e9tica Cl\u00ednica  S\u00e3o Paulo Brazil"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jacqueline","family":"Fonseca","sequence":"additional","affiliation":[{"name":"Laborat\u00f3rio DLE Bioqu\u00edmica Gen\u00e9tica  Rio de Janeiro Brazil"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Zumira A.","family":"Carneiro","sequence":"additional","affiliation":[{"name":"Centro Universit\u00e1rio Est\u00e1cio de Ribeir\u00e3o Preto  S\u00e3o Paulo Brazil"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Beat","family":"Th\u00f6ny","sequence":"additional","affiliation":[{"name":"Division of Metabolism University Children's Hospital  Z\u00fcrich Switzerland"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2021,5,5]]},"reference":[{"key":"e_1_2_8_2_1","doi-asserted-by":"publisher","DOI":"10.1186\/s13023-020-01379-8"},{"key":"e_1_2_8_3_1","doi-asserted-by":"publisher","DOI":"10.1007\/s10545-009-1067-2"},{"key":"e_1_2_8_4_1","doi-asserted-by":"publisher","DOI":"10.1042\/BJ20110293"},{"key":"e_1_2_8_5_1","doi-asserted-by":"publisher","DOI":"10.1055\/s-0038-1673630"},{"key":"e_1_2_8_6_1","doi-asserted-by":"publisher","DOI":"10.1023\/A:1005327313348"},{"key":"e_1_2_8_7_1","doi-asserted-by":"publisher","DOI":"10.1007\/8904_2016_572"},{"key":"e_1_2_8_8_1","doi-asserted-by":"publisher","DOI":"10.1007\/s10545-011-9300-1"},{"key":"e_1_2_8_9_1","doi-asserted-by":"publisher","DOI":"10.1002\/med.10055"},{"key":"e_1_2_8_10_1","doi-asserted-by":"publisher","DOI":"10.1007\/s12519-014-0496-7"},{"key":"e_1_2_8_11_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.braindev.2011.07.009"},{"key":"e_1_2_8_12_1","doi-asserted-by":"publisher","DOI":"10.2174\/1389200024605145"},{"key":"e_1_2_8_13_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ymgme.2017.11.005"},{"key":"e_1_2_8_14_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ajhg.2017.01.002"},{"key":"e_1_2_8_15_1","unstructured":"BlauN BaluyotMM CarducciC SalvaticiE.BIODEFdb International Database of BH4 Deficiencies.http:\/\/www.biopku.org\/biodef\/BIODEF_Results.asp. 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