title: A child with a deletion in the monocarboxylate transporter 8 gene: 7-year follow-up and effects of thyroid hormone treatment.
abstract: OBJECTIVE
  The monocarboxylate transporter 8 (MCT8; SLC16A2) has a pivotal role in neuronal triiodothyronine (T(3)) uptake. Mutations of this transporter determine a distinct X-linked psychomotor retardation syndrome (Allan-Herndon-Dudley syndrome (AHDS)) that is attributed to disturbed thyroid hormone levels, especially elevated T(3) levels. We describe the genetic analysis of the MCT8 gene in a patient suspected for AHDS and the clinical and endocrine effects of L-thyroxine (LT(4)) or liothyronine (LT(3)) treatment intending to overcome the T(3) uptake resistance through alternative transporters.
  
  
  METHODS
  The six exons of the MCT8 gene were amplified individually by PCR. As multiple exons were missing, the length of the X-chromosomal deletion was determined by a dense SNP array, followed by PCR-based fine mapping to define the exact borders of the deleted segment. The clinical and endocrine data of the patient during 6.5 years of LT(4) treatment and two periods (3 months each) of low- and high-dose LT(3) were evaluated.
  
  
  RESULTS
  A partial deletion of the MCT8 gene (comprising five of six exons) was detected, confirming the suspected AHDS. MCT8 dysfunction was associated with partial resistance to T(3) at the hypothalamus and pituitary level, with normal responsiveness at the peripheral organs (liver and cardiovascular system). Thyroid hormone administration had no beneficial effect on the neurological status of the patient.
  
  
  CONCLUSIONS
  We identified a 70 kb deletion encompassing exons 2-6 of the MCT8 gene in our AHDS patient. Both LT(4) and LT(3) administration had no therapeutic effect. Alternatively, treatment of AHDS patients with thyroid hormone analogs should be considered.
authors: Pediatric Endocrinology Unit, Kaplan Medical Center, Affiliated with the Hebrew University of Jerusalem, Rehovot 76100, Israel Department of Internal Medicine, Erasmus MC, Rotterdam, The Netherlands. amzung2@bezeqint.net
authors: Amnon
authors: A
authors: Zung
authors: Theo J
authors: TJ
authors: Visser
authors: André G
authors: AG
authors: Uitterlinden
authors: Fernando
authors: F
authors: Rivadeneira
authors: Edith C H
authors: EC
authors: Friesema
mesh_terms: D002648:Child; D005500:Follow-Up Studies; D017353:Gene Deletion; D006801:Humans; D008297:Male; D038901:X-Linked Intellectual Disability / Q000175:diagnosis / Q000188:drug therapy* / Q000235:genetics*; D027501:Monocarboxylic Acid Transporters / Q000235:genetics*; D009123:Muscle Hypotonia / Q000175:diagnosis / Q000188:drug therapy* / Q000235:genetics*; D009133:Muscular Atrophy / Q000175:diagnosis / Q000188:drug therapy* / Q000235:genetics*; D027981:Symporters; D013963:Thyroid Hormones / Q000097:blood / Q000627:therapeutic use*; D016896:Treatment Outcome
chemical_list: D027501:Monocarboxylic Acid Transporters; C090735:SLC16A2 protein, human; D027981:Symporters; D013963:Thyroid Hormones