{"doi":"10.1002/jimd.12556","title":"A multinational study of acute and long‐term outcomes of Type 1 galactosemia patients who carry the <scp>S135L</scp> (c.<scp>404C</scp> &gt; T) variant of <scp><i>GALT</i></scp>","abstract":"Patients with galactosemia who carry the S135L (c.404C > T) variant of galactose-1-P uridylyltransferase (GALT), documented to encode low-level residual GALT activity, have been under-represented in most prior studies of outcomes in Type 1 galactosemia. What is known about the acute and long-term outcomes of these patients, therefore, is based on very limited data. Here, we present a study comparing acute and long-term outcomes of 12 patients homozygous for S135L, 25 patients compound heterozygous for S135L, and 105 patients homozygous for two GALT-null (G) alleles. This is the largest cohort of S135L patients characterized to date. Acute disease following milk exposure in the newborn period was common among patients in all 3 comparison groups in our study, as were long-term complications in the domains of speech, cognition, and motor outcomes. In contrast, while at least 80% of both GALT-null and S135L compound heterozygous girls and women showed evidence of an adverse ovarian outcome, prevalence was only 25% among S135L homozygotes. Further, all young women in this study with even one copy of S135L achieved spontaneous menarche; this is true for only about 33% of women with classic galactosemia. Overall, we observed that while most long-term outcomes trended milder among groups of patients with even one copy of S135L, many individual patients, either homozygous or compound heterozygous for S135L, nonetheless experienced long-term outcomes that were not mild. This was true despite detection by newborn screening and both early and life-long dietary restriction of galactose. This information should empower more evidence-based counseling for galactosemia patients with S135L.","journal":"Journal of Inherited Metabolic Disease","year":2022,"id":273152,"datarank":0.0,"base_score":0.0,"endowment":0.0,"self_citation_contribution":0.0,"citation_network_contribution":0.0,"self_endowment_contribution":0.0,"citer_contribution":0.0,"corpus_percentile":null,"corpus_rank":null,"citation_count":11,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9296,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2022-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":640249,"name":"Karolina M. 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Estela Rubio‐Gozalbo","orcid":"0000-0001-7182-4056","position":21,"is_corresponding":false},{"id":940183,"name":"Michael Saad‐Naguib","orcid":"0000-0002-6676-6223","position":22,"is_corresponding":false},{"id":940654,"name":"Sabine Scholl‐Buergi","orcid":null,"position":23,"is_corresponding":false},{"id":940184,"name":"Sarah Searcy","orcid":"0000-0003-4883-682X","position":24,"is_corresponding":false},{"id":485351,"name":"Paulo Victor Sgobbi de Souza","orcid":"0000-0002-7416-7108","position":25,"is_corresponding":false},{"id":477386,"name":"Angela Wittenauer","orcid":"0000-0003-1194-4499","position":26,"is_corresponding":false},{"id":373638,"name":"Judith L. Fridovich‐Keil","orcid":"0000-0001-7947-5807","position":27,"is_corresponding":false},{"id":775994,"name":"Quinton S. 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