Monocarboxylate transporter 8 (MCT8) is an active transporter
protein that in humans is encoded by the SLC16A2gene.[5][6][7][8]
Function
MCT8 actively transports a variety of iodo-
thyronines including the thyroid hormones
T3 and
T4.[6]
Clinical significance
A genetic disorder (discovered in 2003[6] and 2004[9]) is caused by mutation in the transporter of thyroid hormone, MCT8, also known as SLC16A2, is believed to be account for a significant fraction of the undiagnosed neurological disorders (usually resulting in
hypotonic/floppy infants with delayed milestones). This genetic defect was known as
Allan–Herndon–Dudley syndrome (since 1944) without knowing its actual cause. It has been shown mutated in cases of X-linked
leukoencephalopathy.[10] Some of the symptoms for this disorder as are follows: normal to slightly elevated
TSH, elevated T3 and reduced T4 (ratio of T3/T4 is about double its normal value). Normal looking at birth and for the first few years, hypotonic (floppy), in particular difficulty to hold the head, possibly difficulty to thrive, possibly with delayed myelination (if so, some cases are reported with an MRI pattern similar to
Pelizaeus–Merzbacher disease, known as PMD[11]), possibly with decreased mitochondrial enzyme activities, possibly with fluctuating
lactate level. Patients have an alert face, a limited IQ, patients may never talk/walk, 50% need feeding tube, patients have a normal life span. This disease can be ruled out with a simple TSH/T4/T3 thyroid test.
Model organisms
Zebrafish
A knockout
zebrafish line was generated in 2014 using the
zinc-finger nuclease (ZFN)-mediated targeted gene editing system.[12] Similar to human patients, the zebrafish larvae exhibited neurological and behavioral deficiencies. They demonstrated reduced locomotor activity, altered
myelin-related genes and neuron-specific deficiencies in circuit formation.[13]
^Tsurusaki Y, Osaka H, Hamanoue H, Shimbo H, Tsuji M, Doi H, Saitsu H, Matsumoto N, Miyake N (Sep 2011). "Rapid detection of a mutation causing X-linked leucoencephalopathy by exome sequencing". Journal of Medical Genetics. 48 (9): 606–9.
doi:
10.1136/jmg.2010.083535.
PMID21415082.
S2CID1157351.
^Vaurs-Barrière C, Deville M, Sarret C, Giraud G, Des Portes V, Prats-Viñas JM, De Michele G, Dan B, Brady AF, Boespflug-Tanguy O, Touraine R (Jan 2009). "Pelizaeus-Merzbacher-Like disease presentation of MCT8 mutated male subjects". Annals of Neurology. 65 (1): 114–8.
doi:
10.1002/ana.21579.
PMID19194886.
S2CID27740314.
^Connors, Kristin A.; Korte, Joseph J.; Anderson, Grant W.; Degitz, Sigmund J. (2010-08-01). "Characterization of thyroid hormone transporter expression during tissue-specific metamorphic events in Xenopus tropicalis". General and Comparative Endocrinology. 168 (1): 149–159.
doi:
10.1016/j.ygcen.2010.04.015.
ISSN1095-6840.
PMID20417208.
Further reading
Halestrap AP, Meredith D (Feb 2004). "The SLC16 gene family-from monocarboxylate transporters (MCTs) to aromatic amino acid transporters and beyond". Pflügers Archiv. 447 (5): 619–28.
doi:
10.1007/s00424-003-1067-2.
PMID12739169.
S2CID15498611.
Friesema EC, Jansen J, Heuer H, Trajkovic M, Bauer K, Visser TJ (Sep 2006). "Mechanisms of disease: psychomotor retardation and high T3 levels caused by mutations in monocarboxylate transporter 8". Nature Clinical Practice Endocrinology & Metabolism. 2 (9): 512–23.
doi:
10.1038/ncpendmet0262.
PMID16957765.
S2CID25232696.
Debrand E, Heard E, Avner P (Mar 1998). "Cloning and localization of the murine Xpct gene: evidence for complex rearrangements during the evolution of the region around the Xist gene". Genomics. 48 (3): 296–303.
doi:
10.1006/geno.1997.5173.
PMID9545634.
Brockmann K, Dumitrescu AM, Best TT, Hanefeld F, Refetoff S (Jun 2005). "X-linked paroxysmal dyskinesia and severe global retardation caused by defective MCT8 gene". Journal of Neurology. 252 (6): 663–6.
doi:
10.1007/s00415-005-0713-3.
PMID15834651.
S2CID31994320.
