Document Detail

Mitochondrial DNA depletion syndromes: review and updates of genetic basis, manifestations, and therapeutic options.
MedLine Citation:
PMID:  23385875     Owner:  NLM     Status:  MEDLINE    
Mitochondrial DNA (mtDNA) depletion syndromes (MDS) are a genetically and clinically heterogeneous group of autosomal recessive disorders that are characterized by a severe reduction in mtDNA content leading to impaired energy production in affected tissues and organs. MDS are due to defects in mtDNA maintenance caused by mutations in nuclear genes that function in either mitochondrial nucleotide synthesis (TK2, SUCLA2, SUCLG1, RRM2B, DGUOK, and TYMP) or mtDNA replication (POLG and C10orf2). MDS are phenotypically heterogeneous and usually classified as myopathic, encephalomyopathic, hepatocerebral or neurogastrointestinal. Myopathic MDS, caused by mutations in TK2, usually present before the age of 2 years with hypotonia and muscle weakness. Encephalomyopathic MDS, caused by mutations in SUCLA2, SUCLG1, or RRM2B, typically present during infancy with hypotonia and pronounced neurological features. Hepatocerebral MDS, caused by mutations in DGUOK, MPV17, POLG, or C10orf2, commonly have an early-onset liver dysfunction and neurological involvement. Finally, TYMP mutations have been associated with mitochondrial neurogastrointestinal encephalopathy (MNGIE) disease that typically presents before the age of 20 years with progressive gastrointestinal dysmotility and peripheral neuropathy. Overall, MDS are severe disorders with poor prognosis in the majority of affected individuals. No efficacious therapy is available for any of these disorders. Affected individuals should have a comprehensive evaluation to assess the degree of involvement of different systems. Treatment is directed mainly toward providing symptomatic management. Nutritional modulation and cofactor supplementation may be beneficial. Liver transplantation remains controversial. Finally, stem cell transplantation in MNGIE disease shows promising results.
Ayman W El-Hattab; Fernando Scaglia
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Publication Detail:
Type:  Journal Article; Review    
Journal Detail:
Title:  Neurotherapeutics : the journal of the American Society for Experimental NeuroTherapeutics     Volume:  10     ISSN:  1878-7479     ISO Abbreviation:  Neurotherapeutics     Publication Date:  2013 Apr 
Date Detail:
Created Date:  2013-04-15     Completed Date:  2013-10-24     Revised Date:  2014-04-01    
Medline Journal Info:
Nlm Unique ID:  101290381     Medline TA:  Neurotherapeutics     Country:  United States    
Other Details:
Languages:  eng     Pagination:  186-98     Citation Subset:  IM    
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MeSH Terms
DNA Replication / genetics,  physiology
DNA, Mitochondrial / genetics*,  metabolism,  physiology*
Liver Transplantation
Mitochondrial Diseases / genetics*,  physiopathology*,  therapy
Mitochondrial Encephalomyopathies / genetics,  pathology,  therapy
Mitochondrial Myopathies / genetics,  pathology,  therapy
Mutation / genetics,  physiology
Nervous System Diseases / genetics*,  physiopathology*,  therapy
Nucleotides / metabolism
Nutritional Support
Thymidine / metabolism
Reg. No./Substance:
0/DNA, Mitochondrial; 0/Nucleotides; VC2W18DGKR/Thymidine

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine

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