title: Novel mutation in MCT8 gene in a Brazilian boy with thyroid hormone resistance and severe neurologic abnormalities.
abstract: MCT8 is a cellular transporter of thyroid hormones important in their action and metabolization. We report a male patient with the novel inactivating mutation 630insG in the coding region in exon 1 of MCT8. He was characterized clinically by severe neurologic impairment (initially with global hypotonia, later evolving with generalized hypertonia), normal growth during infancy, reduced weight gain, and absence of typical signs and symptoms of hypothyroidism, while the laboratory evaluation disclosed elevated T3, low total and free T4, and mildly elevated TSH serum levels. Treatment with levothyroxine improved thyroid hormone profile but was not able to alter the clinical picture of the patient. These data reinforce the concept that the role of MCT8 is tissue-dependent: while neurons are highly dependent on MCT8, bone tissue, adipose tissue, muscle, and liver are less dependent on MCT8 and, therefore, may suffer the consequences of the exposition to high serum T3 levels.
authors.affiliation: Pediatric Endocrinology Unit, Instituto da Criança, Faculdade de Medicina, Universidade de São Paulo, São Paulo, SP, Brazil. hamiltoncm@uol.com.br
authors.forename: Hamilton Cabral de Menezes
authors.initials: HC
authors.lastname: Filho
authors.forename: Suemi
authors.initials: S
authors.lastname: Marui
authors.forename: Thais Della
authors.initials: TD
authors.lastname: Manna
authors.forename: Ester Saraiva
authors.initials: ES
authors.lastname: Brust
authors.forename: Vanessa
authors.initials: V
authors.lastname: Radonsky
authors.forename: Hilton
authors.initials: H
authors.lastname: Kuperman
authors.forename: Vaê
authors.initials: V
authors.lastname: Dichtchekenian
authors.forename: Nuvarte
authors.initials: N
authors.lastname: Setian
authors.forename: Durval
authors.initials: D
authors.lastname: Damiani
mesh_terms: D000595:Amino Acid Sequence / Q000235:genetics; D001927:Brain Diseases / Q000235:genetics* / Q000378:metabolism; D002648:Child; D006801:Humans; D008297:Male; D027501:Monocarboxylic Acid Transporters / Q000235:genetics*; D009122:Muscle Hypertonia / Q000235:genetics; D009123:Muscle Hypotonia / Q000235:genetics; D009154:Mutation / Q000235:genetics*; D027981:Symporters; D018382:Thyroid Hormone Resistance Syndrome / Q000188:drug therapy / Q000235:genetics*; D013974:Thyroxine / Q000627:therapeutic use; D014284:Triiodothyronine / Q000378:metabolism*
chemical_list: D027501:Monocarboxylic Acid Transporters; C090735:SLC16A2 protein, human; D027981:Symporters; D014284:Triiodothyronine; D013974:Thyroxine