Table 1.
Primary mitochondrial classical syndromes with muscle involvement
| DISEASE | INHERITANCE | GENES | MOLECULAR DEFECTS | CLINICAL FEATURES | LABORATORY TESTS | REFERENCES |
|---|---|---|---|---|---|---|
| CPEO | Autosomal dominant, recessive, sporadic (common 4,977 base-pair deletion), or maternally inherited (mtDNA) | POLG1 POLG2 ANT1 C10ORF2 OPA1 TK2 | 1/3 of all single large-scale deletions of mtDNA (4.9-kb) | • Bilateral ophthalmoparesis • Ptosis • Oropharyngeal weakness • Myopathy |
• Detection of mtDNA single deletion or multiple mtDNA deletions with primary nDNA pathogenic variant | [13] |
| MELAS | Maternal inheritance (mtDNA) | MT-TL1 MT-ND5 | 80% of all cases have the m.3243A>G mutation in the MT-TL1 | • Stroke-like episodes, • Myopathy • Encephalopathy with seizures, cognitive impairment, or both |
• Lactic acidemia in blood and CSF • Muscle biopsies with ragged red fibers • MRI Stroke-like lesion(s) |
[16] |
| Kearns-Sayre syndrome | Maternal inheritance (mtDNA), sporadic | Variable deletion ranging from 1.1 to 10 kb | mtDNA single deletions | • Onset before 20 years • Pigmentary retinopathy • CPEO • Myopathy • Cardiac conduction block |
• CSF protein higher than 100 mg/dL • Lactic acidemia in blood and CSF • Muscle biopsy RRF • Cardiac conduction block |
[13] |
| MERRF | Maternal inheritance, sporadic | MT-TK | m.8344A>G | • Myoclonus • Generalized epilepsy • Ataxia • Myopathy |
• CSF protein higher than 100 mg/dL • Lactic acid elevation in blood, CSF, or both |
[20] |
| CoQ10 deficiency | Autosomal recessive | COQ2, COQ4, COQ6, COQ7, COQ8A, COQ8B, COQ9, PDSS1, PDSS2 | CoQ10 biosynthesis defect | • Early infantile onset encephalomyopathy • Steroid-resistant nephrotic syndrome • Multiple-system atrophy-like neurodegenerative phenotype |
• Lactic acidemia in blood and CSF • Muscle biopsies with reduced CoQ10 levels |
[21] |
| TK2 deficiency | Autosomal recessive | TK2 | Cause mitochondrial DNA (mtDNA) maintenance defect | • Infantile-onset myopathy • Juvenile/childhood proximal weakness • Late-onset myopathy with facial and limb weakness |
• Multiple respiratory chain complex deficiency • Reduced mitochondrial DNA content • Elevated CK |
[23, 24] |
CSF: cerebrospinal fluid
RRF: ragged-red fibers
EKG: electrocardiogram
CK: creatine phosphokinase
CPEO: chronic progressive external ophthalmoplegia
MELAS: mitochondrial encephalomyopathy lactic acidosis stroke-like episodes
MERRF: myoclonus epilepsy ragged-red fibers
POLG1 or POLG2: encoding mtDNA-specific polymerase gamma
ANT1: adenine nucleotide translocator1
C10ORF2: encoding a mtDNA helicase called Twinkle
OPA1: Optic atrophy type 1
TK2: Thymidine kinase 2