title: Three novel mutations of the MCT8 (SLC16A2) gene: individual and temporal variations of endocrinological and radiological features.
abstract: We performed genetic analysis and clinical investigations for three patients with suspected monocarboxylate transporter 8 (MCT8) deficiency. On genetic analysis of the MCT8(SLC16A2) gene, novel mutations (c.1333C>A; p.R445S, c.587G>A; p.G196E and c.1063_1064insCTACC; p.R355PfsX64) were identified in each of three patients. Although thyroid function tests (TFTs) showed the typical pattern of MCT8 deficiency at the time of genetic diagnosis in all patients, two patients occasionally were euthyroid. A TRH test revealed low response, exaggerated response and normal response of TSH, respectively. Endocrinological studies showed gonadotropin (Gn) deficiency in two adult patients. On ultrasonography, goiter was detected in one patient. Interestingly, pituitary magnetic resonance imaging (MRI) demonstrated atrophy and thinness of the pituitary gland in two patients. Our findings suggest that thyroid status in patients with MCT8 deficiency varies with time of examination, and repeated TFTs are necessary for patients suspected of MCT8 deficiency before genetic analysis. In addition, it is noteworthy that some variations were observed on the TRH test and ultrasonography of the thyroid gland in the present study. Morphological abnormality of the pituitary gland may be found in some patients, while Gn deficiency should be considered as one of the complications.
authors.affiliation: Department of Pediatrics, The Jikei University School of Medicine, Tokyo, Japan; Department of Pediatrics, Tokyo Metropolitan Kita Medical and Rehabilitation Center for the Disabled, Tokyo, Japan.
authors.forename: Erina
authors.initials: E
authors.lastname: Ono
authors.affiliation: Department of Pediatrics, Tokyo Metropolitan Kita Medical and Rehabilitation Center for the Disabled, Tokyo, Japan.
authors.forename: Masamichi
authors.initials: M
authors.lastname: Ariga
authors.affiliation: Department of Pediatrics, Tokyo Metropolitan Kita Medical and Rehabilitation Center for the Disabled, Tokyo, Japan.
authors.forename: Sakiko
authors.initials: S
authors.lastname: Oshima
authors.affiliation: Department of Pediatrics, Tokyo Metropolitan Kita Medical and Rehabilitation Center for the Disabled, Tokyo, Japan.
authors.forename: Mika
authors.initials: M
authors.lastname: Hayakawa
authors.affiliation: Department of Pediatrics, Tokyo Metropolitan Kita Medical and Rehabilitation Center for the Disabled, Tokyo, Japan.
authors.forename: Masayuki
authors.initials: M
authors.lastname: Imai
authors.affiliation: Department of Pediatrics, Tokyo Metropolitan Kita Medical and Rehabilitation Center for the Disabled, Tokyo, Japan.
authors.forename: Yukikatsu
authors.initials: Y
authors.lastname: Ochiai
authors.affiliation: Department of Endocrinology and Metabolism, Saitama Children's Medical Center, Saitama, Japan.
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Mochizuki
authors.affiliation: Department of Pediatrics, Osaka University Graduate School of Medicine, Osaka, Japan.
authors.forename: Noriyuki
authors.initials: N
authors.lastname: Namba
authors.affiliation: Department of Pediatrics, Osaka University Graduate School of Medicine, Osaka, Japan.
authors.forename: Keiichi
authors.initials: K
authors.lastname: Ozono
authors.affiliation: Department of Pediatrics, The Jikei University School of Medicine, Tokyo, Japan.
authors.forename: Ichiro
authors.initials: I
authors.lastname: Miyata
keywords: Allan-Herndon-Dudley syndrome; MCT8 deficiency; MCT8(SLC16A2) gene; brain MRI; thyroid function