Prenatal Treatment of Thyroid Hormone Cell Membrane Transport Defect Caused by MCT8 Gene Mutation
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Le résumé fourni par la source
Background: Mutations of the thyroid hormone (TH)-specific cell membrane transporter, monocarboxylate transporter 8 ( MCT8 ), produce an X-chromosome-linked syndrome of TH deficiency in the brain and excess in peripheral tissues. The clinical consequences include brain hypothyroidism causing severe psychoneuromotor abnormalities (no speech, truncal hypotonia, and spastic quadriplegia) and hypermetabolism (poor weight gain, tachycardia, and increased metabolism, associated with high serum levels of the active TH, T3). Treatment in infancy and childhood with TH analogues that reduce serum triiodothyronine (T3) corrects hypermetabolism, but has no effect on the psychoneuromotor deficits. Studies of brain from a 30-week-old MCT8-deficient embryo indicated that brain abnormalities were already present during fetal life. Methods: A carrier woman with an affected male child (MCT8 A252fs268*), pregnant with a second affected male embryo, elected to carry the pregnancy to term. We treated the fetus with weekly 500 μg intra-amniotic instillation of levothyroxine (LT4) from 18 weeks of gestation until birth at 35 weeks. Thyroxine (T4), T3, and thyrotropin (TSH) were measured in the amniotic fluid and maternal serum. Treatment after birth was continued with LT4 and propylthiouracil. Follow-up included brain magnetic resonance imaging (MRI) and neurodevelopmental evaluation, both compared with the untreated brother. Results: During intrauterine life, T4 and T3 in the amniotic fluid were maintained above threefold to twofold the baseline and TSH was suppressed by 80%, while maternal serum levels remained unchanged. At birth, the infant serum T4 was 14.5 μg/dL and TSH <0.01 mU/L compared with the average in untreated MCT8-deficient infants of 5.1 μg/ and >8 mU/L, respectively. MRI at six months of age showed near-normal brain myelination compared with much reduced in the untreated brother. Neurodevelopmental assessment showed developmental quotients in receptive language and problem-solving, and gross motor and fine motor function ranged from 12 to 25 at 31 months in the treated boy and from 1 to 7 at 58 months in the untreated brother. Conclusions: This is the first demonstration that prenatal treatment improved the neuromotor and neurocognitive function in MCT8 deficiency. Earlier treatment with TH analogues that concentrate in the fetus when given to the mother may further rescue the phenotype.
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Le contrôle bibliographique ouvert
DOI retrouvé dans Crossref DOI retrouvé, mais le titre doit être comparé manuellement.
- Titre Crossref
- Prenatal Treatment of Thyroid Hormone Cell Membrane Transport Defect Caused by <i>MCT8</i> Gene Mutation
- Date Crossref
- 01/05/2021
- Éditeur
- SAGE Publications
- Type
- journal-article
Ce recoupement confirme des métadonnées liées au DOI. Il ne confirme ni la méthode ni les conclusions de l’étude, et il ne compte pas comme une seconde source scientifique indépendante.
Où se fait cette recherche
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University of Chicago Committees on Genetics pays non établi dans la noticeUniversité ou école supérieure
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University of Illinois Chicago pays non établi dans la noticeUniversité ou école supérieure
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Education Northwest pays non établi dans la noticeUniversité ou école supérieure
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Medical University of South Carolina Department of Radiology and Radiological Science pays non établi dans la noticeUniversité ou école supérieure
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Oregon Health & Science University Department of Pediatrics–Endocrinology and Oregon Health & pays non établi dans la noticeUniversité ou école supérieure
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Doernbecher Children's Hospital pays non établi dans la noticeÉtablissement de santé
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Instituto de Investigaciones Biomédicas Sols-Morreale pays non établi dans la noticeStructure de recherche
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Universidad Autónoma de Madrid pays non établi dans la noticeUniversité ou école supérieure
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University of Miami Department of Medicine pays non établi dans la noticeUniversité ou école supérieure
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Northwest Perinatal Center pays non établi dans la noticeInstitution
Committees on Genetics — University of Chicago, University of Illinois Chicago et Education Northwest, avec 7 autres affiliations.
Une affiliation ne permet pas de déduire la nationalité d’un auteur.