Table 1.
PMD patient characteristics. Abbreviations: CI–CV, OXPHOS complexes I–V; CDG, congenital disorder of glycosylation; CKD, chronic kidney disease; Com, combined; DM, diabetes mellitus; F, female; GDD, global developmental delay; HCM, hypertrophic cardiomyopathy; LTBL, leukocencephalopathy with thalamus and brainstem involvement and high lactate +; M, male; MIU, mors in utero; NALF, neonatal acute liver failure; ND, no data; PEO(+), progressive external ophtalmoplegia (with accompanying symptoms).
| Identifier # | Gene | Mutation | System | Gender | Disease | Symptoms | Age of Onset (years) | Current Age (years) | Age at Death (years) | Diagnostic Score (/8, see Table S1) |
|---|---|---|---|---|---|---|---|---|---|---|
| 45 | TMEM126B | c.401het_delA (p.134N>IIefs*2), c.635G>T (p.212G>V) | Cl | M | Myopathy | 11 | 40 | 6 | ||
| 30 | ACAD9 | c.976G>C (p.326A>T), c.1552C> T (p.518R>C) | Cl | F | Hypertrophic cardiomyopathy | HCM | 2 | 8 | 6 | |
| 33 | MT-ND1 | mtDNA.3481G>A (p.59E>K) | Cl | F | GDD, cardiomyopathy, lactic acidosis | 0 | 2 | 8 | ||
| 48 | ND6 | mtDNA.14487T>C (p.63E*) | Cl | M | Acute vision loss, progressive myoclonic epilepsy with extrapyramidal syndrome and psychosis | 19 | 43 | 7 | ||
| 2737 | NDUFS1 | c.1057G>C (p.353A>P), c.420+2T>C (splice site mutation) | Cl | M | Leigh syndrome | GDD, neurocognitive regression | 2 | 3 | 8 | |
| 2736 | NDUFS2 | Homozygous: c.1336G>A (p.446D>N) | Cl | F | Leigh syndrome | Necrotic encephalopathy after vaccination | 0 | 0 | 6 | |
| 2497 | NDUFA13 AND PGM1 | NDUFA13, homozygous: c.170G>A(p.57R>H), PGM1, homozygous: c.1108A>T (p.370K*) | CI | F | Leigh syndrome/CDG | Deafness, GDD, spastic dystonic quadriplegia, epilepsy | 0.5 | 17 | 8 | |
| 52 | SURF1 | c.312del10 insAT (p.fs*), c.544 GT>CA (p.182V>H) | CIV | F | Leigh syndrome | Ataxia, myopathy, respiratory insufficiency | 1 | 8 | 8 | |
| 55 | SURF1 | c.845-856del (p.282S>Cfs*), c.870insA (p.292K>E) | CIV | F | Leigh syndrome | Ataxia, dystrophy, FTT, renal tubular acidosis | 2 | 3 | 8 | |
| 2264 | MT-ATP6 | mtDNA.8993T>G (p.156L>R) | CV | M | Infantile NARP | GDD, ataxia, epilepsy, dystrophy | 1 | 19 | 8 | |
| 47 | AGK | c.409C>T (p.137R>X), c.1131+5G>A (splice site exon 15) | Com OXPHOS | M | Sengers syndrome | Congenital cataract, HCM, myopathy | 0 | 23 | 8 | |
| 34 | EARS2 | c.286G>A (p.96Q>K), c.500G>A (p.167C>Y) | Com OXPHOS | M | LTBL | GDD | 1 | 12 | 7 | |
| 43 | MRPL44 | ND | Com OXPHOS | M | Myopathy, cardiomyopathy, encephalopathy with epilepsy | 1 | 33 | 5 | ||
| 42 | Large mtDNA deletion | mtDNA.12113_14421del2309 | Com OXPHOS | F | Kearns-sayre | Bilateral ptosis, scoliosis, myopathy, ophtalmoplegia | 16 | 63 | 2 | |
| 41 | Large mtDNA deletion | mtDNA.8937_14422del | Com OXPHOS | F | PEO+ | Ptosis, PEO, dysphagia, myopathy | 12 | 63 | 6 | |
| 50 | MT-TD | mtDNA.7526A>G | Com OXPHOS | F | Myopathy, migraine | 9 | 36 | 6 | ||
| 36 | MT-TE | mtDNA.14674T>G | Com OXPHOS | F | GDD, metabolic decompensations, CKD | 0 | 15 | 4 | ||
| 57 | MT-TE | mtDNA.14709T>C | Com OXPHOS | F | Hypotonia, GDD, DM | 0 | 14 | 7 | ||
| 58 | MT-TL1 | mtDNA.3291T>C | Com OXPHOS | F | Myopathy, respiratory failure (on ventilation), DM, CKD , HCM | 41 | 73 | 4 | ||
| 123 | MT-TL1 | mtDNA.3261A>G | Com OXPHOS | F | Myopathy, exercice intolerance, lactic acidosis, sudden death during respiratory infection at home | 1 | 33 | 7 | ||
| 53 | MT-TL1 | mtDNA.3243A>G | Com OXPHOS | M | MELAS | Cardiopathy, DM, deafness, frontal syndrome, myopathy, ophthalmoplegia | 41 | 61 | 8 | |
| 54 | MT-TL1 | mtDNA.3243A>G | Com OXPHOS | F | MELAS | Exercice intolerance, lactic acidosis, epilepsy | 10 | 35 | 6 | |
| 72 | MT-TL1 | mtDNA.3243A>G | Com OXPHOS | M | MELAS | DM, epilepsy, pseudo-strokes, deafness | 30 | 42 | 8 | |
| 40 | MT-TL1 | mtDNA.3243A>G | Com OXPHOS | F | MELAS | DM, deafness, HCM, weight loss, CKD, biliary cysts | 40 | 72 | 4 | |
| 51 | MT-TN | mtDNA.5728A>G | Com OXPHOS | M | Growth hormone deficiency, CKD, GDD, epilepsy, myopathy | 2.3 | 17 | 8 | ||
| 124 | TWNK | Heterozygous c.1358G>C (p.453R>P), WT | Com OXPHOS | M | PEO+ | Myopathy with external ophtalmoplegia | 42 | 55 | 3 | |
| 35 | POLG | c.1402A>G(p.468N>D), WT | Com OXPHOS | F | Alpers | Liver fibrosis, ataxia, spastic hemiparesis | 38 | 58 | 7 | |
| 38 | POLG | c.1399G>A (p.467A>T), c.2542G>A (P.848G>S) | Com OXPHOS | F | Alpers | NALF, refractory epilepsy | 1 | 1.5 | 7 | |
| 120 | POLG | c.1252T>G (p.418C>G), WT | Com OXPHOS | M | Myopathy | 56 | 81 | 3 | ||
| 59 | ATAD3 | c.1582C>T (p.528R>W), WT | Structural | F | GDD, Spastic dystonic quadriplegia, morphea | 1 | 7 | 6 | ||
| 2130 | PDHA1 | c.904C>T (302R>C), WT | TCA cycle | F | GDD, spastic dystonic quadriplegia, epilepsy | 0.6 | 40 | 6 | ||
| 31 | PDHA1 | c.523G>A (p.175A>T), WT | TCA cycle | F | Deafness, infantile spasms, GDD | 0 | 6 | 8 | ||
| 128 | SLC25A42 | Homozygous c.309C>G (p.103Y>X) | TCA cycle | M | Myopathy, acidocetosis | 9 | 28 | 7 | ||
| 2738 | SLC25A42 | Homozygous c.871A>G (p. 291N>D) | TCA cycle | M | GDD, lactic acidosis, severe spastic quadriplegia, dysarthria, severe kyphosis, epilepsy | <5 | 30 | 6 |