Table 1 Details on genotype, phenotype, diet intervention, safety and efficacy of all 20 cases split into cases with and without epilepsy
From: Ketogenic diet for mitochondrial disease: a systematic review on efficacy and safety
Author and year (reference) | Involved Gene | MD subgroup | Age start KD (y) | Gender | Composition KD | Ketosis | KD duration (m) | Reason stop KD | Supplements | Development* | Muscles and movement* | Other signs and symptoms* | Adverse events | Positive effects on |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
Cases with epilepsy | ||||||||||||||
Köse 2020 [36] | FBXL4 (AR) | Unclear function | 0.8 | M | NR |  +  | 0.2 (5d) | AE | B, CoQ, R, T | DD | TD | Visual impairment, bowel dysmotility bleeding, dysphagia, FP | Metabolic acidosis | NR |
O'Byrne 2018 [46] | MTO1 (AR) | DNA, RNA and protein synthesis/RNA metabolism | 7 | F | CKD 4,75:1–2:1 | NR |  > 108 | NA | CA, CoQ, D, E, R, T | DD | MW, TD, ataxia | behavioural issues | Sudden deterioration during flu-like illness (visual impairment, ptosis, generalised weakness) | E (temporary seizure reduction for 4 y) |
Steriade, 2014 [58] | MT-TL1 (maternal) | DNA, RNA and protein synthesis/tRNA | 22 | F | MAD | NR |  > 12 | NA | ALA, BC, CA,CoQ, CR, D, E, FA | NR | NR | Migraine, stroke like episodes |  | E (seizure free for > 1 y), stroke like episodes (resolved) |
Joshi 2009 [33] | POLG (AR) | DNA, RNA and protein synthesis/Replication | 4.6 | F | CKD 4:1 | NR | 9 | AE | NR | DD | MW, gait ataxia | Visual impairment | Death (at age 66Â m) | E (temporary seizure free for 7Â m), muscle (bladder/bowel control regained, walking with assistance regained), development (ability to speak) |
Spiegler 2011 [34] | POLG (AR) | DNA, RNA and protein synthesis/Replication | 3.6 | F | CKD | NR | 3 | AE | NR | DD | ataxia | Bowel obstruction, dysphagia | Death (at age 46Â m) | E (temporary seizure free for a few w) |
Koessler 2021 [35] | POLG (AR) | DNA, RNA and protein synthesis/Replication | 16 | F | CKD 4:1 |  +  | 3 | AE | CoQ, R, T | NR | NR | Migraine | Death (at age 16 y) | E (temporary improvement of status epilepticus for 3 w) |
Pfeiffer 2020 [43] | SLC25A12 (AR) | Substrate/Carrier | 1.8 | M | CKD 4:1 | NR |  > 4 | NA | NR | DD | TD | NR |  | E (seizure free for > 4 m, TD (improved head and neck control) |
SLC25A12 (AR) | Substrate/Carrier | 6 | F | CKD 3–4:1 |  +  |  > 20 | NA | NR | DD | TD | NR |  | E (seizure free for > 20 m), TD (improved head and neck control) development, (psychomotor, social interaction), MRI | |
Cases without epilepsy | ||||||||||||||
Della-Marina, 2020 [41] | BCS1L (AR) | Assembly, complex II | 7 | F | MAD |  +  | 4 | PD | NR | NR | NR | Hearing loss, alopecia, sparse, brittle hair |  | Hair growth |
Illsinger, 2020 [45] | ECHS1 (AR) | Inhibitors | 4 | F | MAD 1:1 | NR |  > 60 | NA | B, T | NR | dystonia | NR | Worsening of MRI | Movement disorder (resolved) |
Kotecha, 2019 [37] | LRPPRC (AR) | DNA, RNA and protein synthesis/RNA metabolism | 0 (7d) | F | CKD |  +  | 3.3 | AE | NR | NR |  | Respiratory distress | Progressive hypotonia and regression, weight loss | NR |
Ahola, 2016 [38] | mtDNA single del (maternal) | mtDNA single deletion | 62 | F | MAD |  +  | 0.1 (4d) | AE | NR | NR | MW, EI, ptosis | NR | RM, headache, tiredness | NR |
Ahola, 2016 [38] | mtDNA single del (maternal) | mtDNA single deletion | 36 | F | MAD |  +  | 0.3 (8d) | AE | NR | NR | MW, EI, ptosis | NR | RM, headache, tiredness | NR |
Deberles, 2020 [42] | MT-TW (maternal) | t-RNA | 3 | F | CKD 3:1 |  +  |  > 96 | NA | C, CA, E, R, T | DD | MW, CM | FTT |  | Muscle (regained walking, improved limb muscle strength), cardiomyopathy (resolved), weight gain, growth |
Laugel 2007 [40] | NDUFV1 (AR) | OXPHOS enzymes/complex I | 0.8 | M | CKD 3:1 |  +  | 24 | PD | CoQ, R | DD | MW, TD, ptosis, ataxia, pyramidal signs | Vomiting, hyperpnea, strabismus |  | CPEO, ptosis (resolved) |
Huang 2017 [39] | SUCLA2 (AR) | DNA, RNA and protein synthesis/Nucleotides | 1.3 | M | CKD 3:1 |  +  | 5 | AE | C, CA, CoQ, E, R, T | DD | MW, TD ptosis, hyper-reflexia | Hearing loss, FTT, FP, GER, constipation | Severe lethargy | Lactate (normalised) |
Fraser 2014 [32] | TPK1 (AR) | Cofactors/Thiamine | 1.7 | M | CKD 3:1 |  +  |  > 9 | NA | ALA, B, N, T | DD | TD | FP |  | TD (improved head and neck control, truncal tone stability), development (increased verbal response and social interaction), food intake |
Ahola, 2016 [38] | TWNK (AR), mult del (maternal) | DNA, RNA and protein synthesis/Replication | 54 | M | MAD |  +  | 0.3 (9d) | AE | NR | NR | MW, EI, ptosis | NR | RM, headache, tiredness | NR |
Ahola, 2016 [38] | TWNK (AR), mult del (maternal) | DNA, RNA and protein synthesis/Replication | 52 | M | MAD |  +  | 0.3 (8d) | AE | NR | NR | MW, EI, ptosis | NR | RM, headache, tiredness | NR |
Ahola, 2016 [38] | TWNK (AR), mult del (maternal) | DNA, RNA and protein synthesis/Replication | 40 | m | MAD |  +  | 0.4 (11d) | AE | NR | NR | MW, EI, ptosis | NR | RM, headache, tiredness | NR |