{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,10]],"date-time":"2026-06-10T15:02:55Z","timestamp":1781103775329,"version":"3.54.1"},"reference-count":39,"publisher":"National Academy of Sciences","issue":"45","content-domain":{"domain":["www.pnas.org"],"crossmark-restriction":true},"short-container-title":["Proc. Natl. Acad. Sci. U.S.A."],"published-print":{"date-parts":[[2011,11,8]]},"abstract":"<jats:p>\n                    Pentosuria is one of four conditions hypothesized by Archibald Garrod in 1908 to be inborn errors of metabolism. Mutations responsible for the other three conditions (albinism, alkaptonuria, and cystinuria) have been identified, but the mutations responsible for pentosuria remained unknown. Pentosuria, which affects almost exclusively individuals of Ashkenazi Jewish ancestry, is characterized by high levels of the pentose sugar\n                    <jats:sc>l<\/jats:sc>\n                    -xylulose in blood and urine and deficiency of the enzyme\n                    <jats:sc>l<\/jats:sc>\n                    -xylulose reductase. The condition is autosomal-recessive and completely clinically benign, but in the early and mid-20th century attracted attention because it was often confused with diabetes mellitus and inappropriately treated with insulin. Persons with pentosuria were identified from records of Margaret Lasker, who studied the condition in the 1930s to 1960s. In the\n                    <jats:italic>DCXR<\/jats:italic>\n                    gene encoding\n                    <jats:sc>l<\/jats:sc>\n                    -xylulose reductase, we identified two mutations,\n                    <jats:italic>DCXR c.583\u0394C<\/jats:italic>\n                    and\n                    <jats:italic>DCXR c.52(+1)G &gt; A<\/jats:italic>\n                    , each predicted to lead to loss of enzyme activity. Of nine unrelated living pentosuric subjects, six were homozygous for\n                    <jats:italic>DCXR c.583\u0394C<\/jats:italic>\n                    , one was homozygous for\n                    <jats:italic>DCXR c.52(+1)G &gt; A<\/jats:italic>\n                    , and two were compound heterozygous for the two mutant alleles.\n                    <jats:sc>l<\/jats:sc>\n                    -Xylulose reductase was not detectable in protein lysates from subjects\u2019 cells and high levels of xylulose were detected in their sera, confirming the relationship between the\n                    <jats:italic>DCXR<\/jats:italic>\n                    genotypes and the pentosuric phenotype. The combined frequency of the two mutant\n                    <jats:italic>DCXR<\/jats:italic>\n                    alleles in 1,067 Ashkenazi Jewish controls was 0.0173, suggesting a pentosuria frequency of approximately one in 3,300 in this population. Haplotype analysis indicated that the\n                    <jats:italic>DCXR c.52(+1)G &gt; A<\/jats:italic>\n                    mutation arose more recently than the\n                    <jats:italic>DCXR c.583\u0394C<\/jats:italic>\n                    mutation.\n                  <\/jats:p>","DOI":"10.1073\/pnas.1115888108","type":"journal-article","created":{"date-parts":[[2011,11,1]],"date-time":"2011-11-01T00:21:08Z","timestamp":1320106868000},"page":"18313-18317","update-policy":"https:\/\/doi.org\/10.1073\/pnas.cm10313","source":"Crossref","is-referenced-by-count":16,"title":["Garrod's fourth inborn error of metabolism solved by the identification of mutations causing pentosuria"],"prefix":"10.1073","volume":"108","author":[{"given":"Sarah B.","family":"Pierce","sequence":"first","affiliation":[{"name":"Department of Medicine, Division of Medical Genetics, and"},{"name":"Department of Genome Sciences, University of Washington, Seattle, WA 98195-7720;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Cailyn H.","family":"Spurrell","sequence":"additional","affiliation":[{"name":"Department of Medicine, Division of Medical Genetics, and"},{"name":"Department of Genome Sciences, University of Washington, Seattle, WA 98195-7720;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jessica B.","family":"Mandell","sequence":"additional","affiliation":[{"name":"Department of Medicine, Division of Medical Genetics, and"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ming K.","family":"Lee","sequence":"additional","affiliation":[{"name":"Department of Medicine, Division of Medical Genetics, and"},{"name":"Department of Genome Sciences, University of Washington, Seattle, WA 98195-7720;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sharon","family":"Zeligson","sequence":"additional","affiliation":[{"name":"Medical Genetics Institute, Shaare Zedek Medical Center, Jerusalem 91031, Israel; and"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Michael S.","family":"Bereman","sequence":"additional","affiliation":[{"name":"Department of Genome Sciences, University of Washington, Seattle, WA 98195-7720;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sunday M.","family":"Stray","sequence":"additional","affiliation":[{"name":"Department of Medicine, Division of Medical Genetics, and"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Siv","family":"Fokstuen","sequence":"additional","affiliation":[{"name":"Genetic Medicine, University Hospitals of Geneva, 1211 Geneva 4, Switzerland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Michael J.","family":"MacCoss","sequence":"additional","affiliation":[{"name":"Department of Genome Sciences, University of Washington, Seattle, WA 98195-7720;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ephrat","family":"Levy-Lahad","sequence":"additional","affiliation":[{"name":"Medical Genetics Institute, Shaare Zedek Medical Center, Jerusalem 91031, Israel; and"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mary-Claire","family":"King","sequence":"additional","affiliation":[{"name":"Department of Medicine, Division of Medical Genetics, and"},{"name":"Department of Genome Sciences, University of Washington, Seattle, WA 98195-7720;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Arno G.","family":"Motulsky","sequence":"additional","affiliation":[{"name":"Department of Medicine, Division of Medical Genetics, and"},{"name":"Department of Genome Sciences, University of Washington, Seattle, WA 98195-7720;"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"341","published-online":{"date-parts":[[2011,10,31]]},"reference":[{"key":"e_1_3_3_1_2","first-page":"214","article-title":"The Croonian lectures on inborn errors of metabolism, lecture IV","volume":"2","author":"Garrod AE","year":"1908","unstructured":"AE Garrod, The Croonian lectures on inborn errors of metabolism, lecture IV. 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