Table 1.
Clinical Features and Findings Associated with the Five Most Common Pathogenic MT‐ATP6 Variants
| m.8993T>C | m.8993T>G | m.9035T>C | m.9176T>C | m.9185T>C | |
|---|---|---|---|---|---|
| Demographic data | |||||
| No. of patients | 24 | 22 | 8 | 11 | 18 |
| F/M | 10/14 | 8/14 | 5/3 | 6/5 | 7/11 |
| No. of pedigrees | 20 | 19 | 3 | 5 | 9 |
| No. of deceased | 4 | 5 | 1 | 2 | 3 |
| Median age, yr (range, IQR) | 27.5 (3–74, 38.8) | 30 (0.75–59, 39) | 24 (10–48, 23) | 15.5 (2–49, 19.5) | 25 (19–54, 29) |
| Median age of onset, yr (range, IQR) | 5.5 (0.5–71, 22.3) | 2 (0–34, 11.1) | 10 (3–19, 15.3) | 1 (1–32, 3.9) | 6 (2–15, 8) |
| Clinical findings | |||||
| LS | 8/23 | 11/17 | 2/8 | 6/11 | 3/18 |
| UMN signs | 9/20 | 10/14 | 4/8 | 6/10 | 10/16 |
| Learning disability | 14/18 | 6/8 | 5/7 | 5/9 | 9/16 |
| Seizures | 6/22 | 9/20 | 0/8 | 3/8 | 0/18 |
| Dystonia | 3/24 | 3/20 | 1/8 | 3/10 | 0/17 |
| Ataxia | 20/22 | 10/11 | 8/8 | 6/10 | 12/17 |
| Neuropathya | 15/17 | 4/6 | 3/7 | 5/10 | 14/14 |
| Pes cavus | 9/22 | 1/12 | 2/3 | 4/11 | 7/12 |
| RPb | 3/18 | 12/13 | 2/7 | 1/9 | 0/13 |
| Cardiac | 2/17 | 3/9 | 0/4 | 2/8 | 0/11 |
| DM | 0/22 | 1/14 | 0/6 | 1/11 | 1/11 |
| MRI head changes | |||||
| Cerebellar atrophy | 9/14 | 7/13 | 4/7 | 1/8 | 5/10 |
| BG changes | 8/14 | 8/13 | 1/7 | 3/8 | 3/10 |
| Brainstem | 5/14 | 0/13 | 1/7 | 2/8 | 0/7 |
Denominator values vary due to missing data.
Reports of the nerve conduction studies were available for 26 patients. The most common finding was axonal, sensory‐motor neuropathy (23/26), followed by mixed axonal and demyelinating neuropathy (2/26), and only a single patient with the m.8993T>C variant had demyelinating neuropathy.
χ2 test (Bonferroni correction; p ≤ 0.006) showed a higher proportion of patients with the m.8993T>G mutation had RP compared to patients harboring either the m.8993T>C (92% vs 17%, p < 0.001) or m.9176T>C (92% vs 11%, p = 0.001) variants.
BG = basal ganglia; DM = diabetes mellitus; F = female; IQR = interquartile range; LS = Leigh syndrome; M = male; MRI = magnetic resonance imaging; RP = retinitis pigmentosa; UMN = upper motor neuron sign defined as the presence of pathological brisk reflexes and/or positive Babinski sign.