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, 3M2F, 7M3F, 5M2F, 3M3F, 3M12F, 3M
Age of onset (years)b1–229.6 (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)b38.6 (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,d132.5 (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)

SporadicAD or AR, DMPK, ZNF9, CAPN3, PABPN1, SMN1, TIA1 or unknown
Histological findings in skeletal muscleNone

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 consequencesMtDNA depletion in brain and liverMtDNA depletion, small amount of heteroplasmic multiple mtDNA deletions in skeletal muscleHeteroplasmic multiple mtDNA deletions, or single large mtDNA deletion in skeletal muscleHeteroplasmy; ~70% of mutant mtDNA in muscle and urine epithelial cellsMultiple mtDNA deletionsNone
Muscle symptoms−/++++++++
Clinical symptomsChildhood‐onset ataxia, neuropathy, athetosis, hearing loss, epilepsy, hepatopathyAtaxia, neuropathy, epilepsy, psychiatric symptoms, cognitive decline, obesity/insulin resistanceMitochondrial myopathy, ptosis, progressive external ophthalmoplegia, exercise intoleranceMitochondrial myopathy, cardiomyopathy, diabetes mellitus, hearing loss, stroke‐like episodesDistal 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).

  • = 0.009, = 0.002 (nonparametric Kruskal–Wallis test).