Mitochondrial dementia: A sporadic case of progressive cognitive and behavioral decline with hearing loss due to the rare m.3291T>C MELAS mutation

• Published in: Journal of the neurological sciences 2011-01, Vol.300 (1), p.165-168
• Main Authors: Salsano, Ettore, Giovagnoli, Anna Rita, Morandi, Lucia, Maccagnano, Carmelo, Lamantea, Eleonora, Marchesi, Chiara, Zeviani, Massimo, Pareyson, Davide
• Format: Article
• Language: English
• Subjects: Adult; Biological and medical sciences; Cognition Disorders - complications; Cognition Disorders - genetics; Degenerative and inherited degenerative diseases of the nervous system. Leukodystrophies. Prion diseases; Dementia; Dementia - complications; Dementia - genetics; Female; Hearing loss; Hearing Loss - complications; Hearing Loss - genetics; Humans; Medical sciences; MELAS syndrome; MELAS Syndrome - genetics; Mitochondrial disorders; Mutation; Neurology; Olanzapine; RNA, Transfer, Leu - genetics; Wolff-Parkinson-White Syndrome - complications; Wolff–Parkinson–White syndrome
• ISSN: 0022-510X; 1878-5883
• DOI: 10.1016/j.jns.2010.09.022

Abstract We report the case of a 23-year-old Italian female harboring the rare m.3291T>C mutation in the MT-TL1 gene, that encodes the mitochondrial transfer RNA for leucine 1 (UUA/G). MT-TL1 mutations usually cause the MELAS (mitochondrial encephalomyopathy, lactic acidosis and stroke-like episodes) syndrome. Our patient, however, suffered from a non-syndromic mitochondrial disorder (MID), clinically characterized by progressive cognitive and behavioral decline, and hearing loss; brain MRI disclosed diffuse supratentorial and infratentorial atrophy; EKG revealed a Wolff–Parkinson–White syndrome; combined neuroleptic and antidepressant treatment markedly improved her behavioral symptoms. This case expands the clinical spectrum of non-syndromic MIDs, and further confirms that no obvious genotype–phenotype correlation exists for the m.3291T>C DNA mutation; indeed, this mutation has been previously reported in a Japanese child, who suffered from MELAS, and in an Italian child, who presented an apparently isolated mild myopathy. Moreover, it supports the hypothesis that at least in MT-TL1 -related MIDs, dementia may be caused by a progressive neurodegenerative process, rather than by injury accumulation due to stroke-like episodes. Finally, our case suggests that common neuroleptic and antidepressant drugs may be clinically efficacious in the management of psychiatric symptoms associated with MIDs.