好色先生

好色先生

Explore the latest content from across our publications
Join The AAN

Log In

Forgot Password?
Create New Account

Loading... please wait

Abstract Details

TK2 Mutation Presenting as Indolent Myopathy
Muscle Disease/Neuromuscular Junction
P07 - (-)
026
BACKGROUND: Recessive mutations in the TK2 gene typically cause fatal infantile mitochondrial DNA (mtDNA) depletion syndromes. However, the progression of weakness may vary, as shown by recently described adult cases. To date, only five adult patients with TK2-related MDS have been reported.
DESIGN/METHODS: We describe a 22 years-old man presenting muscle weakness. We review the history of present illness and the physical exam. A complete work-up focused on neuromuscular disorders was performed including serum CK level, electromyography, nerve conduction studies, brain MRI, muscle imaging, muscle biopsy and molecular study.
RESULTS: Clinically, he was weak as a child but sought medical attention as an adult. An episode of aspiration pneumonia led to respiratory arrest, after which the weakness worsened rapidly. The patient is now wheelchair-bound, with bulbar, facial and axial weakness and a striking gynecomastia. CK level was 757 IU/l and venous lactic acid was normal. Endocrine and cardiological work-ups, also nerve conduction studies were normal. Muscle tomography showed widespread and severe fatty degeneration of the muscles. A muscle biopsy showed dystrophic features, up to 50% of fibers were COX-negative, and most were ragged-blue fibers. Electron microscopy showed mitochondrial paracrystalline inclusions.The activity of complex I was 35% of normal. Long-range PCR showed mtDNA multiple deletions. Real-time PCR showed a mild reduction of the mtDNA:nuclear DNA ratio in muscle. Sequencing of the TK2 gene disclosed a previously reported homozygous c.323C>T, p.T108M mutation. A double-trouble was ruled out by inmmunohistochemistry and molecular studies.
CONCLUSIONS: This report expands the clinical spectrum of TK2-related diseases, emphasizing that can cause dystrophic features in adult patients with mitochondrial myopathy, which should alert neurologists to the correct molecular diagnosis. The degree of mtDNA depletion could play an important role in the clinical manifestations.
Authors/Disclosures
Carmen Paradas Lopez, MD, PhD
PRESENTER 		No disclosure on file
Purificacion Gutierrez Rios, PhD (Columbia University) No disclosure on file
Federica Agosta (San Raffaele Scientific Institute) Federica Agosta has received personal compensation in the range of $500-$4,999 for serving on a Speakers Bureau for Philips. Federica Agosta has received personal compensation in the range of $500-$4,999 for serving as an Editor, Associate Editor, or Editorial Advisory Board Member for Elsevier INC.
No disclosure on file
No disclosure on file
Michio Hirano, MD, FAAN (Columbia University Medical Center) Dr. Hirano has received personal compensation in the range of $500-$4,999 for serving as a Consultant for UCB Biopharma SRL. Dr. Hirano has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Precision Biosciences. Dr. Hirano has received personal compensation in the range of $10,000-$49,999 for serving on a Scientific Advisory or Data Safety Monitoring board for UCB Biopharma SRL. Dr. Hirano has received personal compensation in the range of $5,000-$9,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Apollo Communication. Dr. Hirano has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Envision Communications. Dr. Hirano has received personal compensation in the range of $500-$4,999 for serving on a Speakers Bureau for 好色先生. Dr. Hirano has received personal compensation in the range of $500-$4,999 for serving on a Speakers Bureau for Cure SMA. Dr. Hirano has received personal compensation in the range of $500-$4,999 for serving on a Speakers Bureau for Muscular Dystrophy Association. The institution of Dr. Hirano has received research support from UCB. The institution of Dr. Hirano has received research support from Cyclerion. The institution of Dr. Hirano has received research support from Astellas. The institution of Dr. Hirano has received research support from Tisento Therapeutics. The institution of Dr. Hirano has received research support from Stealth Biotherapeutics. The institution of Dr. Hirano has received research support from Abliva. Dr. Hirano has received intellectual property interests from a discovery or technology relating to health care. Dr. Hirano has received intellectual property interests from a discovery or technology relating to health care. Dr. Hirano has received personal compensation in the range of $0-$499 for serving as a Study Section Reviewer with NIH. Dr. Hirano has a non-compensated relationship as a Research Advisory Board member with Muscular Dystrophy Association that is relevant to AAN interests or activities. Dr. Hirano has a non-compensated relationship as a Scientific and Medical Advisory Board member with United Mitochondrial Disease Foundation that is relevant to AAN interests or activities. Dr. Hirano has a non-compensated relationship as a Scientific Advisory Board member with Barth Syndrome Foundation that is relevant to AAN interests or activities.
No disclosure on file