Table 1 Clinical summary of patients (* indicates those patients included in the microarray analysis)
Patient | Onset | Main clinical symptoms | Age at biopsy | Genetics | Respiratory chain enzymes activities | Muscle pathology | References |
|---|---|---|---|---|---|---|---|
*P1 | 2 y | Hypotonia, weakness, progressive gait impairment. Unable to stand. CK 2200U/L | 2 y | 96% mtDNA depletion Hom A181V TK2 | N/A | Dystrophic, severe COX reduction. No RRF. Type 1 predominance | Family 1 P2 Galbiati et al., 2006 [12] |
*P2 | 3 y | Hypotonia, weakness, walking difficulties, exercise intolerance, ptosis, ophthalmoplegia, cerebellar vermis atrophy. CK 523U/L | 4 y | 92% mtDNA depletion het C108W + L257P TK2 | Complex I, III and IV deficiency | Dystrophic, COX negative fibres (74%). RRF (68%). Moderate increase intracellular lipid. Type 1 predominance | Family 2 P2 Galbiati et al., 2006 [12] |
*P3 | 2 y | Unstable gait, muscle hypotrophy. CK 800 U/L | 2 y | 90% mtDNA depletion, Hom A181V TK2 | Complex I, III, IV and V deficiency | Dystrophic, COX negative fibres. Increased intracellular lipids | Pat E Spinazzola et al., 2009 [11] |
*P4 | 2 y | Unstable gait, muscle hypotrophy. CK 1000U/L | 2 y | 90% mtDNA depletion, Hom A181V TK2 | Complex I, III, IV and V deficiency | Dystrophic, COX negative fibres. Increased intracellular lipids | Pat C Spinazzola et al. 2009 [11] |
*P5 | 5 y | Low stature, lactic acidosis hypothyroidism, retinitis pigmentosa. | 6 y | 6331-13994 (7.7Â kb) 64% mtDNA | Normal | RRF | Â |
*P6 | 7 y | Retinitis pigmentosa leukoenchephalopathy deafness | 9 y | 11033-15157 70% | CI-CIII/CIII | RRF | Pineda et al., 2006 |
*P7 | 30 y | Retinitis pigmentosa deafness, ataxia, myopathy, heart conduction defects. | 30 y | 6331-13994 77% mtDNA molecules | Normal | RRF | Â |
*P8 | 15 y | PEO, pigmentary degeneration of retina, complete AV block and myopathy | 31 y | 8.4Â kDa deletion; 35% mtDNA molecules | N/A | COX negative fibres and RRF. | Â |
P9 | 30 y | Eyelid ptosis | 38 y | 4.8Â kDa mtDNA deletion; 40% molecules | N/A | COX negative fibres and RRF. | Â |
P10 | 4 m | Delayed motor milestones, hypotonia, dystonia, severe axial muscle weakness, brisk deep tendon reflex and mild spasticity in lower limbs. Neurosensorial deafness. Mild methyl malonic aciduria | 7 m | 87% mtDNA depletion het. p.G350S + p.G350V SUCLA 2 | Complex II, III and IV deficiency | Generalized COX reduction. No RRF. Moderate increase intracellular lipids |  |
P11 | 1.5 y | Proximal muscle weakness, mildly elevated CK levels. | 4 and 5 y | 95% mtDNA depletion het. p.T77M + p. R161K TK2 | Normal | COX negative fibres. Type 1 predominance | Wang et al., 2005; Vilá et al., 2008 [8] and 2010 |
P12 | 10Â yrs | Exercise intolerance, myalgia, lactic acidosis, eyelid ptosis, CK 400U/L, hypertrophic cardiomyopathy, epilepsy | 13 y | A3243G tRNA-LEU mtDNA | N/A | RRF | Â |