{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,1]],"date-time":"2026-09-01T00:16:50Z","timestamp":1788221810814,"version":"build-2803163510"},"reference-count":24,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2021,11,10]],"date-time":"2021-11-10T00:00:00Z","timestamp":1636502400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Pediatr."],"abstract":"<jats:p><jats:bold>Background:<\/jats:bold> There are only a few case reports and small case series on neonatal-onset Dubin\u2013Johnson syndrome (DJS), particularly from Far-East Asia, Iranian and Moroccan Jews, and Europe.<\/jats:p><jats:p><jats:bold>Objectives:<\/jats:bold> In this first study from the Arabs and the largest series reported to date, we characterized the clinical, laboratory, and molecular features and outcome of gene-confirmed neonatal-onset DJS.<\/jats:p><jats:p><jats:bold>Methods:<\/jats:bold> We reviewed our database of 533 cases of neonatal cholestasis that presented to our center during the period from 2008 to 2019. We identified neonates with a disease-causing mutation in <jats:italic>ABCC2<\/jats:italic> gene.<\/jats:p><jats:p><jats:bold>Results:<\/jats:bold> Twenty-eight neonates with DJS were diagnosed (5.3%). All of the 28 were full-term, well looking neonates without hepatosplenomegaly, with cholestasis, and normal liver synthetic function since the 1 week of life that resolved within 3\u20136 months of age, followed by a benign course punctuated by recurrent episodes of jaundice in 43% during a median follow up period of 9.25 (range 2.5\u201314 years). Alanine aminotransferase levels were within normal range in 26 patients (92%) and mildly elevated in two patients. ALT levels were significantly lower in neonates with DJS than in other cases with neonatal cholestasis from other causes (<jats:italic>p<\/jats:italic> &amp;lt; 0.001). The median urinary coproporphyrin I% was 88% (IQ1\u2013IQ3 = 84.2\u201392.7%). We identified four homozygous variants in the <jats:italic>ABCC2<\/jats:italic> gene (from 22 unrelated families), one splicing variant (c.3258+1G&amp;gt;A; p.?), and three were missense variants; two of which were novel missense variants [c.1594G&amp;gt;A (p.Glu532Lys) and c.2439G&amp;gt;C (p.Lys813Asn)]. The p.Gly758Val mutation has occurred in 23 patients (from 19 unrelated families).<\/jats:p><jats:p><jats:bold>Conclusions:<\/jats:bold> Our study suggests that normal ALT-cholestasis in a well-looking neonate should trigger evaluation for DJS. The p.Gly758Val variant in ABCC2 is the most predominant mutation among Arabs with \u201cfounder effects.\u201d Identification of the predominant <jats:italic>ABCC2<\/jats:italic> variant in any population is likely to facilitate rapid molecular analysis by future targeting of that specific mutation.<\/jats:p>","DOI":"10.3389\/fped.2021.741835","type":"journal-article","created":{"date-parts":[[2021,11,10]],"date-time":"2021-11-10T09:45:59Z","timestamp":1636537559000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":9,"title":["Clinical, Biochemical, and Molecular Characterization of Neonatal-Onset Dubin\u2013Johnson Syndrome in a Large Case Series From the 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