Abstract
We previously reported two unrelated boys aged 3 and 8 years with mutations in the thyroid hormone transporter gene MCT8 resulting in severe global retardation and an uncommon pattern of thyroid hormone abnormalities. We now further describe an unusual neurological phenotype associated with these mutations, namely paroxysmal kinesigenic dyskinesias (PKD), provoked by certain stimuli including changing of their clothes or diapers. It is not clear how the MCT8 defect causes PKDs. PKDs have been previously noted in patients with thyroid abnormalities. This novel X–linked condition widens the spectrum of secondary PKDs.
This is a preview of subscription content, log in via an institution to check access.
Similar content being viewed by others
References
Abe T, Suzuki T, Unno M, Tokui T, Ito S (2002) Thyroid hormone transporters: recent advances. Trends Endocrinol Metab 13:215–220
Bernal J (2002) Action of thyroid hormone in brain. J Endocrinol Invest 25:268–288
Bhatia KP (1999) The paroxysmal dyskinesias. J Neurol 246:149–155
Blakeley J, Jankovic J (2002) Secondary paroxysmal dyskinesias. Mov Disord 17:726–734
Boyages SC (2000) The neuromuscular system and brain in hypothyroidism. In: Braverman LE, Utider RD (eds) Werner and Ingbar’s the thyroid: a fundamental and clinical text. Lippincott Williams and Wilkins, Philadelphia, pp 803–810
Delong GR, Tai M, Xue–Yi C, Xin–Min J, Zhi–Hong D, Rakeman MA, Ming–Li Z, Heinz R (1994) The neuromotor deficit in endemic cretinism. In: Stanbury JB (ed) The damaged brain of iodine deficiency. Cognizant Communication, New York, pp 9–13
Demirkiran M, Jankovic J (1995) Paroxysmal dyskinesias: clinical features and classification. Ann Neurol 38:571–579
Drake ME Jr (1987) Paroxysmal kinesigenic choreoathetosis in hyperthyroidism. Postgrad Med J 63:1089–1090
Dumitrescu AM, Liao XH, Best TB, Brockmann K, Refetoff S (2004) A novel syndrome combining thyroid and neurological abnormalities is associated with mutations in a monocarboxylate transporter gene. Am J Hum Genet 74:168–175
Fischbeck KH, Layzer RB (1979) Paroxysmal choreoathetosis associated with thyrotoxicosis. Ann Neurol 6:453–454
Friesema EC, Ganguly S, Abdalla A, Manning Fox JE, Halestrap AP, Visser TJ (2003) Identification of monocarboxylate transporter 8 as a specific thyroid hormone transporter. J Biol Chem 278:40128–40135
Friesema ECH, Grueters A, Biebermann H, Krude H, von Moers A, Reeser M, Barrett TG, Mancilla EE, Svensson J, Kester MHA, Kuiper GGJM, Balkassmi S, Uitterlinden AG, Koehrle J, Rodien P, Halestrap AP, Visser TJ (2004) Association between mutations in a thyroid hormone transporter and severe X–linked psychomotor retardation. Lancet 364:1435–1437
Halpern JP, Boyages SC, Maberly GF, Collins JK, Eastman CJ, Morris JG (1991) The neurology of endemic cretinism. A study of two endemias. Brain 114:825–841
Hennemann G, Docter R, Friesema EC, de Jong M, Krenning EP, Visser TJ (2001) Plasma membrane transport of thyroid hormones and its role in thyroid hormone metabolism and bioavailability. Endocr Rev 22:451–476
Jankovic J, Demirkiran M (2002) Classification of paroxysmal dyskinesias and ataxias. Adv Neurol 89:387–400
Marsden CD, Quinn NP (1990) The dystonias. BMJ 300:139–144
Meyer BU, Irlbacher K, Meierkord H (2001) Analysis of stimuli triggering attacks of paroxysmal dystonia induced by exertion. J Neurol Neurosurg Psychiatry 70:247–251
Plant GT, Williams AC, Earl CJ, Marsden CD (1984) Familial paroxysmal dystonia induced by exercise. J Neurol Neurosurg Psychiatry 47:275–279
Puri V, Chaudhry N (2004) Paroxysmal kinesigenic dyskinesia manifestation of hyperthyroidism. Neurol India 52:102–103
Yen DJ, Shan DE, Lu SR (1998) Hyperthyroidism presenting as recurrent short paroxysmal kinesigenic dyskinesia. Mov Disord 13:361–363
Author information
Authors and Affiliations
Corresponding author
Additional information
K. B. and A. M. D. contributed equally to this work.
Rights and permissions
About this article
Cite this article
Brockmann, K., Dumitrescu, A.M., Best, T.T. et al. X–linked paroxysmal dyskinesia and severe global retardation caused by defective MCT8 gene. J Neurol 252, 663–666 (2005). https://doi.org/10.1007/s00415-005-0713-3
Received:
Revised:
Accepted:
Published:
Issue Date:
DOI: https://doi.org/10.1007/s00415-005-0713-3