Dystonia as a presenting feature of the 3243 mitochondrial DNA mutation

Abstract

A variety of neurologic phenotypes have been described in patients with mitochondrial disorders. We report a 32‐year‐old man in whom dystonia was the salient and presenting feature of a mitochondrial DNA mutation. He presented at age 23 with writer's cramp and progressed over 5 years to exhibit dystonia in facial muscles and lower limbs. He also has exercise intolerance, mild, bilateral ptosis, proximal muscle weakness, and sensorineural hearing loss. Molecular genetic analysis of blood, urine, and muscle biopsy demonstrated the presence of a heteroplasmic point mutation at nucleotide position 3243. The 3243 mtDNA mutation has pleomorphic manifestations, and dystonia should be added to the list of associated clinical features.

Movement disorders and inborn errors of metabolism in adults: A diagnostic approach

“…Leigh syndrome is genetically and biochemically heterogeneous and has been reported in association with complex I, complex IV and complex V defects (Hanna and Bhatia 1997). Dystonia has been also reported in association with the primary LHON mutations G14459A, T14459A, T14596A, and G11778A, with or without blindness (Jun et al 1994;Shoffner et al 1995;De Vries et al 1996;McFarland et al 2007), the MELAS mutation A3243G (Sudarsky et al 1999) and in association with Kearns-Sayre syndrome (Marie et al 1999). A novel C4716G mutation has been described recently in patients with dystonia, bilateral basal ganglia lesions, epilepsy, and ptosis (McFarland et al 2007).…”

Mitochondrial DNA mutations in complex I and tRNA genes in Parkinson’s disease

“…Although the specific mtDNA mutations that account for the complex I deficiency have yet to be identified in PD, 5-7 extrapyramidal features, particularly dystonia, have been reported in association with several mtDNA mutations. [14][15][16] Furthermore, a family with atypical parkinsonism associated with neuronal loss in the substantia nigra was found to harbor the most common primary mutation of Leber's hereditary optic neuropathy (LHON) (at nucleotide position [np] 11778), demonstrating an association between an inherited mtDNA mutation and parkinsonism with nigral cell loss. 17 To identify mtDNA mutations that might influence the risk of developing PD, we sequenced the mtDNA-encoded complex I genes and transfer RNA (tRNA) molecules in 28 PD patients and 8 control subjects, and screened for selected mtDNA mutations in up to 243 additional PD patients and up to 209 additional control subjects.…”

Multiple Neurologic, Psychiatric, and Endocrine Complaints in a Young Woman: A Case Discussion and Review of the Clinical Features and Management of Mitochondrial Myopathy, Encephalopathy, Lactic Acidosis, and Stroke

“…4 Dystonias, or abnormal sustained postures, may also be presenting features of mitochondrial disorders such as MELAS (as with patients who have a 3243 mutation and present initially with muscle cramps, then develop proximal muscle weakness, exercise intolerance, ptosis, and sensorineural hearing loss). 5 The differential of congenital dystonia in young adults is broad and includes doparesponsive dystonia (which is more common in females and often mistaken for juvenile-onset Parkinson's disease, but is more responsive to low-dose levodopa than is Parkinson's disease), myoclonic dystonia (with rapid jerks instead of sustained abnormal postures), idiopathic and focal torsion dystonia, cerebral palsy, Huntington's disease, Parkinson's disease, and psychogenic dystonia. Other associated features of each of these diagnoses, including birth history of children (e.g., anoxia leading to cerebral palsy), an autosomal dominant pattern (as in idiopathic dystonia and Huntington's disease), and psychiatric symptoms (e.g., la belle indifference in conversion disorder), may help rule out mitochondrial disorders.…”