Article

1 H Magnetic Resonance Spectroscopy in Monocarboxylate Transporter 8 Gene Deficiency

Department of Radiology, University Medical Center Groningen and University of Groningen, Hanzeplein 1, Groningen, The Netherlands.
Journal of Clinical Endocrinology &amp Metabolism (Impact Factor: 6.31). 06/2008; 93(5):1854-9. DOI: 10.1210/jc.2007-2441
Source: PubMed

ABSTRACT In monocarboxylate transporter 8 (MCT8) gene deficiency, a syndrome combining thyroid and neurological abnormalities, the central nervous system has not yet been characterized by magnetic resonance (MR) spectroscopy.
We studied whether the degree of dysmyelinization in MCT8 gene deficiency according to MR imaging (MRI) is coupled with abnormalities in brain metabolism.
MRI and MR spectroscopy of the brain were performed twice in two MCT8 gene deficiency patients, for the first time at age 8-10 months and for the second time at age 17-28 months. The results were compared with those obtained in controls of a similar age.
Compared with controls, young children with MCT8 show choline and myoinositol level increases and N-acetyl aspartate decreases in supraventricular gray and white matter, phenomena associated with the degree of dysmyelinization according to MRI.
MCT8 gene deficiency results in deviant myelinization and general atrophy, which is substantiated by the MR spectroscopy findings of increased choline and myoinositol levels and decreased N-acetyl aspartate. The observations suggest that different mutations in the MCT8 gene lead to differences in the severity of the clinical spectrum, dysmyelinization, and MR spectroscopy-detectable changes in brain metabolism.

0 Followers
 · 
111 Views
 · 
0 Downloads
  • Source
    • "MCT8 is expressed in the blood-brain barrier (BBB), the choroid plexuses and the plasma membrane of neural cells [5]. MCT8 gene mutations cause an X-linked syndrome combining severe neurodevelopmental impairment and abnormal distribution and metabolism of thyroid hormones [6]–[18]. The syndrome manifests in infants as early as two months of age. "
    [Show abstract] [Hide abstract]
    ABSTRACT: Mutations of the monocarboxylate transporter 8 (MCT8) cause a severe X-linked intellectual deficit and neurological impairment. MCT8 is a specific thyroid hormone (T4 and T3) transporter and the patients also present unusual abnormalities in the serum profile of thyroid hormone concentrations due to altered secretion and metabolism of T4 and T3. Given the role of thyroid hormones in brain development, it is thought that the neurological impairment is due to restricted transport of thyroid hormones to the target neurons. In this work we have investigated cerebral metabolism in mice with Mct8 deficiency. Adult male mice were infused for 30 minutes with (1-(13)C) glucose and brain extracts prepared and analyzed by (13)C nuclear magnetic resonance spectroscopy. Genetic inactivation of Mct8 resulted in increased oxidative metabolism as reflected by increased glutamate C4 enrichment, and of glutamatergic and GABAergic neurotransmissions as observed by the increases in glutamine C4 and GABA C2 enrichments, respectively. These changes were distinct to those produced by hypothyroidism or hyperthyroidism. Similar increments in glutamate C4 enrichment and GABAergic neurotransmission were observed in the combined inactivation of Mct8 and D2, indicating that the increased neurotransmission and metabolic activity were not due to increased production of cerebral T3 by the D2-encoded type 2 deiodinase. In conclusion, Mct8 deficiency has important metabolic consequences in the brain that could not be correlated with deficiency or excess of thyroid hormone supply to the brain during adulthood.
    PLoS ONE 10/2013; 8(10):e74621. DOI:10.1371/journal.pone.0074621 · 3.23 Impact Factor
  • Source
    • "In addition to the clinical and biological features of patients with SLC16A2 mutations, some authors have reported a nonspecific myelination delay [Holden et al., 2005; Namba et al., 2008] and spectroscopic abnormalities [Sijens et al., 2008]. More recently, the identification of SLC16A2 mutations in a series of patients initially considered as presenting with a severe Pelizaeus–Merzbacher-like disease (PMD) in their first years of life has confirmed this association with delayed myelination [Gika et al., 2010; Vaurs - Barrì ere et al., 2009] . "
    [Show abstract] [Hide abstract]
    ABSTRACT: SLC16A2, the gene for the 2(nd) member of the solute carrier family 16 (monocarboxylic acid transporter), located on chromosome Xq13.2, encodes a very efficient thyroid hormone (TH) transporter: monocarboxylate transporter 8, MCT8. Its loss of function is responsible in males for a continuum of psychomotor retardation ranging from severe (no motor acquisition, no speech) to mild (ability to walk with help and a few words of speech). Triiodothyronine uptake measurement in transfected cells and, more recently, patient fibroblasts, has been described to study the functional consequences of MCT8 mutations. Here we describe 3 novel MCT8 mutations, including one missense variation not clearly predicted to be damaging but found in a severely affected patient. Functional studies in fibroblasts and JEG3 cells demonstrate the usefulness of both cellular models in validating the deleterious effects of a new MCT8 mutation if there is still a doubt as to its pathogenicity. Moreover, the screening of fibroblasts from a large number of patient fibroblasts and of transfected mutations has allowed us to demonstrate that JEG3 transfected cells are more relevant than fibroblasts in revealing a genotype-phenotype correlation.
    Human Mutation 07/2013; 34(7). DOI:10.1002/humu.22331 · 5.05 Impact Factor
  • [Show abstract] [Hide abstract]
    ABSTRACT: Iterative feedback tuning (IFT) is a data-based method for the tuning of restricted complexity controllers. At each iteration, an update for the parameters of the controller is estimated from data obtained partly from the normal operation of the closed loop system and partly from a special experiment. The choice of a prefilter for the input data to the special experiment is a degree of freedom of the method. In the present contribution, the prefilter is designed in order to enhance the accuracy of the IFT update.
    Decision and Control, 2003. Proceedings. 42nd IEEE Conference on; 01/2004
Show more

Preview

Download
0 Downloads