Table 1.
Characteristics of mitochondrial and non‐mitochondrial neuromuscular disease patients
| IOSCA (N = 5a) | MIRAS (N = 9) | PEO (N = 8) | MELAS/MIDD (N = 5) | IBM (N = 6) | NMD (N = 15) | |
|---|---|---|---|---|---|---|
| Gender (n) | 2F, 3M | 2F, 7M | 3F, 5M | 2F, 3M | 3F, 3M | 12F, 3M |
| Age of onset (years)b | 1–2 | 29.6 (18.0–44.0) | 27.8 (21.0–35.0) | 39.3 (30.0–48.0) | 61.4 (49.0–83.0) | 26.3 (2.0–60.0) |
| Age at sampling (years)b | 38.6 (33.0–42.0) | 41.2 (21–52.0) | 50.0 (39.0–57.0) | 54.0 (39.0–68.0) | 71.0 (58.0–85.0) | 49.9 (23.0–77.0) |
| FGF21 (pg/ml)c , d | – | 132.5 (51.0–279.8) | 454.0 (222.0–604.3)† | 562.0 (188.5 –2569.0)‡ | 57.0 (34.3–287.8) | 114.0 (24.0–190.0) |
| Inheritance disease gene, amino acid change |
AR, TWNK
p. Y508C |
AR, POLG
p. W748S+E1143G |
AD, TWNK 13AA dup (TWNK‐PEO); AR, POLG p. A1105T/N468D (POLG‐PEO); Sporadic, mtDNA single deletion (Del‐PEO) |
Maternal, mtDNA m.3243A>G, tRNALeu(UUR) |
Sporadic | AD or AR, DMPK, ZNF9, CAPN3, PABPN1, SMN1, TIA1 or unknown |
| Histological findings in skeletal muscle | None |
1–5% COX‐/SDH+ fibres |
POLG/TWNK‐PEO: 5–12% COX‐/SDH+; Del‐PEO: 30–60% COX‐/SDH+ |
5–30% COX‐/SDH+ fibres |
1–8% COX‐/SDH+ fibres |
Dystrophy, hypertrophy, normal respiratory chain |
| MtDNA consequences | MtDNA depletion in brain and liver | MtDNA depletion, small amount of heteroplasmic multiple mtDNA deletions in skeletal muscle | Heteroplasmic multiple mtDNA deletions, or single large mtDNA deletion in skeletal muscle | Heteroplasmy; ~70% of mutant mtDNA in muscle and urine epithelial cells | Multiple mtDNA deletions | None |
| Muscle symptoms | − | −/+ | + | ++ | ++ | ++ |
| Clinical symptoms | Childhood‐onset ataxia, neuropathy, athetosis, hearing loss, epilepsy, hepatopathy | Ataxia, neuropathy, epilepsy, psychiatric symptoms, cognitive decline, obesity/insulin resistance | Mitochondrial myopathy, ptosis, progressive external ophthalmoplegia, exercise intolerance | Mitochondrial myopathy, cardiomyopathy, diabetes mellitus, hearing loss, stroke‐like episodes | Distal progressive muscle weakness |
−, muscle phenotype not present; +, mild muscle phenotype; ++, primary muscle phenotype. AR, autosomal recessive; AD, autosomal dominant; COX‐/SDH+, cytochrome C oxidase‐negative/succinate dehydrogenase‐positive fibres; F, female; M, male; N, number; mtDNA, mitochondrial DNA.
See Dataset EV1 for raw data.
aAdditional IOSCA child patient (four years of age; Fig 2B). This patient, however, was not included in the overall statistical analysis due to lack of appropriate age‐ and gender‐matched control samples.
bValues represent mean with minimal and maximal age.
cValues represent median with interquartile range.
dNormal value for FGF21 ≤ 331 pg/ml (Lehtonen et al, 2016).
‡ P = 0.009, † P = 0.002 (nonparametric Kruskal–Wallis test).