Clinical spectrum of mitochondrial DNA depletion due to mutations in the thymidine kinase 2 gene.

Abstract

BACKGROUND:

Mitochondrial DNA depletion syndrome is an autosomal recessive disorder characterized by decreased mitochondrial DNA copy numbers in affected tissues. It has been linked to 4 genes involved in deoxyribonucleotide triphosphate metabolism: thymidine kinase 2 (TK2), deoxyguanosine kinase (DGUOK), polymerase gamma (POLG), and SUCLA2, the gene encoding the beta-subunit of the adenosine diphosphate-forming succinyl coenzyme A synthetase ligase.

OBJECTIVE:

To highlight the variability in the clinical spectrum of TK2-related mitochondrial DNA depletion syndrome.

DESIGN:

Review of patients and the literature.

SETTING:

Tertiary care university.

PATIENTS:

Four patients with mitochondrial DNA depletion syndrome and mutations in the TK2 gene.

MAIN OUTCOME MEASURES:

Definition of clinical variability.

RESULTS:

Patient 1 had evidence of lower motoneuron disease and was initially diagnosed as having spinal muscular atrophy type 3. Patient 2, who is alive and ambulatory at age 9 years, presented at age 2 years with a slowly progressive mitochondrial myopathy. Patient 3 had a more severe myopathy, with onset in infancy and death at age 6 years of respiratory failure. Patient 4 had a rapidly progressive congenital myopathy with rigid spine syndrome and he died at age 19 months.

CONCLUSION:

The clinical spectrum of TK2 mutations is not limited to severe infantile myopathy with motor regression and early death but includes spinal muscular atrophy type 3-like presentation, rigid spine syndrome, and subacute myopathy without motor regression and with longer survival.

• Authors: Maryam Oskoui, Guido Davidzon, Juan Pascual, Ricardo Erazo, Juliana Gurgel-Giannetti, Sindu Krishna, Eduardo Bonilla, Darryl C De Vivo, Sara Shanske, Salvatore DiMauro
• Journal: Archives of neurology (Arch Neurol) Vol. 63 Issue 8 Pg. 1122-6 (Aug 2006) ISSN: 0003-9942 [Print] United States
• PMID: 16908738 (Publication Type: Case Reports, Journal Article, Review)

Chemical References

• DNA, Mitochondrial
• thymidine kinase 2
• Thymidine Kinase

Topics

• Adolescent
• Child
• DNA, Mitochondrial (genetics, metabolism)
• Female
• Humans
• Infant
• Male
• Mitochondrial Diseases (enzymology, genetics, pathology)
• Mutation
• Thymidine Kinase (genetics, metabolism)