Adult cases of mitochondrial DNA depletion due to TK2 defect

Abstract

TK2 mutations can cause mitochondrial myopathy with a slow progression. Comparison of patients with similar mutations but different disease progression might address potential mechanisms of mtDNA maintenance modulation.

TK2 mutation presenting as indolent myopathy

“…This adult case of indolent myopathy expands the clinical spectrum of TK2-related diseases. Five recently published adult cases revealed that TK2-related MDS can have early onset and slow progression worsening in adulthood, 6 as in our case, or it can present in adulthood. 5 All patients showed muscle involvement, including bulbar, facial, and axial weakness, whereas respiratory insufficiency seemed confined to the early-onset cases.…”

“…[1][2][3] However, the progression of weakness may vary, 4 as shown by recently described adult patients with late-onset myopathy. 5,6 To date, only 5 adult patients with TK2-related MDS have been reported. Herein, we describe a man who had several unusual features.…”

Mitochondrial DNA Depletion Syndromes: Review and Updates of Genetic Basis, Manifestations, and Therapeutic Options

“…Other, less common, presentations include spinal muscular atrophylike presentation [13] and chronic progressive external ophthalmoplegia with proximal muscle weakness [23]. Milder presentations have been reported and include late onset proximal muscle weakness [15], adult-onset progressive myopathy [22], and sensorineural hearing loss [21].…”

“…mtDNA content is typically severely reduced in muscle tissue. Electron transport chain (ETC) activity assays in skeletal muscle typically show decreased activity of multiple complexes with complex I, I + III, and IV being the most affected [13][14][15][16][17][18][19][20][21][22][23].…”

Unsolved issues related to human mitochondrial diseases

“…The presence of modifying factors could however be demonstrated in diseases due to mutations of the POLG or TK2 nuclear genes and of the mtDNA-encoded ND1, ND4 and ND6 genes causing Leber Hereditary Optic Neuropathy (LHON). They were proposed to underlie the absence of symptoms despite the presence of the mutations in LHON [4] or to significantly modify the presentation in the case of POLG or TK2 [5,6].…”