{
  "abstract": "Classic galactosemia (CG) is a potentially lethal disease that results from profound deficiency of galactose-1-P uridylyltransferase (GALT). Prior reports document elevated galactose metabolites beginning in utero in CG, raising concern that long-term complications in CG might also trace their origins to the prenatal period. However, studies document that elevated galactose metabolites in the postnatal period do not predict later developmental complications, challenging the connection. Here, we explored the relationship between elevated galactose metabolites in utero and fetal outcome using a GALT-null rat model of CG. To modify galactose metabolites in utero, we arranged rat crosses to produce GALT-null pups developing within either a GALT-null or heterozygous dam, and with or without heterozygous siblings. We reasoned that GALT activity present outside the fetus, but within the maternal-fetal compartment, might limit metabolic abnormalities in a developing GALT-null fetus -- and it did. Specifically, while galactose metabolites in GALT-null fetal pups from all crosses remained elevated over controls, the levels varied. When the dam and some siblings were heterozygous, amniotic fluid galactitol from GALT-null fetal pups at GD21 was comparable to the levels reported from second trimester human CG amniotic fluid. When the dam was GALT-null, but some siblings were heterozygous, the median galactitol level in amniotic fluid was 2.45-fold higher. When the dam and all siblings were GALT-null, the median amniotic fluid galactitol level was 5.67-fold higher. GALT-null fetal pups also showed significant growth delay in utero, but only when the dam and all siblings were GALT-null. That growth of GALT-null fetal pups was fully rescued by gestation within a heterozygous dam despite the persistence of moderately elevated galactose metabolites raises the possibility that babies with CG developing within a carrier mother might also be at least partially protected in utero from the adverse consequences of their GALT-deficiency. Author summary: Metabolic abnormalities in classic galactosemia can be detected in utero, raising concern that long-term complications might also trace their origins to the prenatal period. Here, we addressed the relationship between prenatal metabolic abnormality and phenotypic consequence using a GALT-null rat model for classic galactosemia. Our results demonstrate that partial metabolic rescue conferred by developing within a heterozygous dam fully rescues the growth delay otherwise seen in GALT-null fetal pups. This finding challenges the connection between moderate prenatal metabolic abnormality and complications in CG.",
  "abstract_shown": true,
  "affiliations": [
    "Department of Human Genetics, Emory University School of Medicine, Atlanta, Georgia, United States of America",
    "Emory College of Arts and Sciences, Emory University, Atlanta, Georgia, United States of America"
  ],
  "article_type": "Research Article",
  "arxiv": null,
  "author_total": 10,
  "authors": [
    {
      "affs": [
        0
      ],
      "name": "Shauna A. Rasmussen"
    },
    {
      "affs": [
        1
      ],
      "name": "Catherine M. Lemons"
    },
    {
      "name": "Madelyn M. Seemiller"
    },
    {
      "name": "Sabrina R. Dallas"
    },
    {
      "name": "Milan Cambon Ledesma"
    },
    {
      "name": "Yuhan Wu"
    },
    {
      "name": "Lauren E. Anshen"
    },
    {
      "name": "Ashlyn Farnham"
    },
    {
      "name": "Olivia S. Garrett"
    },
    {
      "name": "Judith L. Fridovich-Keil"
    }
  ],
  "bibtex": "https://research.draconitic.com/paper/63m3ffvebrw53.bib",
  "cited_by": 0,
  "doi": "10.1371/journal.pgen.1012276",
  "fulltext_url": "https://journals.plos.org/plosgenetics/article?id=10.1371/journal.pgen.1012276",
  "id": "63m3ffvebrw53",
  "issns": [
    "1553-7404"
  ],
  "landing_url": "https://journals.plos.org/plosgenetics/article?id=10.1371/journal.pgen.1012276",
  "language": null,
  "licence": "CC-BY-4.0",
  "licence_label": "CC BY 4.0",
  "licence_source": "journal",
  "licence_url": "https://creativecommons.org/licenses/by/4.0/",
  "metadata_licence": null,
  "native_subjects": [
    [
      "openalex",
      "1308|Metabolism and Genetic Disorders"
    ],
    [
      "plos",
      "/Biology and life sciences/Anatomy/Body fluids/Amniotic fluid"
    ],
    [
      "plos",
      "/Biology and life sciences/Anatomy/Body fluids/Blood/Blood plasma"
    ],
    [
      "plos",
      "/Biology and life sciences/Biochemistry/Enzymology/Enzyme chemistry/Enzyme metabolism"
    ],
    [
      "plos",
      "/Biology and life sciences/Biochemistry/Metabolism/Metabolites"
    ],
    [
      "plos",
      "/Biology and life sciences/Genetics/Heredity/Heterozygosity"
    ],
    [
      "plos",
      "/Biology and life sciences/Physiology/Body fluids/Amniotic fluid"
    ],
    [
      "plos",
      "/Biology and life sciences/Physiology/Body fluids/Blood/Blood plasma"
    ],
    [
      "plos",
      "/Medicine and health sciences/Anatomy/Body fluids/Amniotic fluid"
    ],
    [
      "plos",
      "/Medicine and health sciences/Anatomy/Body fluids/Blood/Blood plasma"
    ],
    [
      "plos",
      "/Medicine and health sciences/Women's health/Maternal health/Birth"
    ],
    [
      "plos",
      "/Medicine and health sciences/Women's health/Maternal health/Pregnancy"
    ],
    [
      "plos",
      "/Medicine and health sciences/Women's health/Obstetrics and gynecology/Birth"
    ],
    [
      "plos",
      "/Medicine and health sciences/Women's health/Obstetrics and gynecology/Pregnancy"
    ],
    [
      "plos",
      "/Physical sciences/Chemistry/Chemical compounds/Organic compounds/Carbohydrates/Monosaccharides/Galactose"
    ],
    [
      "plos",
      "/Physical sciences/Chemistry/Organic chemistry/Organic compounds/Carbohydrates/Monosaccharides/Galactose"
    ]
  ],
  "openalex": "W7213924924",
  "pdf_url": "https://journals.plos.org/plosgenetics/article/file?id=10.1371/journal.pgen.1012276&type=printable",
  "pmcid": null,
  "pmid": null,
  "published": "2026-09-21",
  "publisher": "Public Library of Science",
  "ris": "https://research.draconitic.com/paper/63m3ffvebrw53.ris",
  "sources": [
    {
      "first_seen": "2026-10-30T12:17:43Z",
      "native_id": "10.1371/journal.pgen.1012276",
      "source": "plos",
      "url": "https://journals.plos.org/plosgenetics/article?id=10.1371/journal.pgen.1012276"
    }
  ],
  "subjects": [
    {
      "field": "medicine",
      "origin": "plos:anatomy",
      "subfield": "physiology"
    },
    {
      "field": "medicine",
      "origin": "plos:women's health",
      "subfield": "reproductive-child"
    }
  ],
  "title": "Prenatal consequences of GALT deficiency in a rat model of classic galactosemia",
  "title_text": "Prenatal consequences of GALT deficiency in a rat model of classic galactosemia",
  "type": "peer-reviewed",
  "updated_at": "2026-10-30T12:17:43Z",
  "url": "https://research.draconitic.com/paper/63m3ffvebrw53",
  "venue": "PLOS Genetics",
  "versions": []
}