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These concepts were transferred to other inborn errors of metabolism and led to significant reduction in morbidity and to an improvement in quality of life. Important milestones were the successful development of a low\u2010phenylalanine diet for phenylketonuria patients, the recognition of tetrahydrobiopterin as an option to treat these individuals pharmacologically, and finally market approval of this drug. The work related to the discovery of a pharmacological treatment led metabolic researchers and pediatricians to new insights into the molecular processes linked to mutations in the phenylalanine hydroxylase gene at the cellular and structural level. Again, phenylketonuria became a prototype disorder for a previously underestimated but now rapidly expanding group of diseases: protein misfolding disorders with loss of function. Due to potential general biological mechanisms underlying these disorders, the door may soon open to a systematic development of a new class of pharmaceutical products. These pharmacological chaperones are likely to correct misfolding of proteins involved in numerous genetic and nongenetic diseases.<\/jats:p>","DOI":"10.1007\/s10545-010-9185-4","type":"journal-article","created":{"date-parts":[[2010,9,7]],"date-time":"2010-09-07T12:05:37Z","timestamp":1283861137000},"page":"649-658","source":"Crossref","is-referenced-by-count":29,"title":["Phenylketonuria as a model for protein misfolding diseases and for the development of next generation orphan drugs for patients with inborn errors of metabolism"],"prefix":"10.1002","volume":"33","author":[{"given":"Ania C.","family":"Muntau","sequence":"first","affiliation":[{"name":"Dr. von Hauner Children's Hospital, Department of Molecular Pediatrics Ludwig Maximilians University Lindwurmstrasse 4 Munich 80337 Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"S\u00f8ren W.","family":"Gersting","sequence":"additional","affiliation":[{"name":"Dr. von Hauner Children's Hospital, Department of 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