Table 1
Demographics and common clinical findings of patients with POLG-related cerebellar ataxia (N = 184).
| MEDIAN (RANGE) OR n (%) | ||
|---|---|---|
| Demographics | ||
| Age at onset (years) | 25 (4–77) | |
| Age at diagnosis (years) | 43 (9–80) | |
| Gender | female | 100 (54.3%) |
| male | 55 (29.8%) | |
| n/a | 29 (15.8%) | |
| Pathogenic variant | W748S (POLG1) | 93 (38.3%)* |
| A467T (POLG1) | 65 (26.7%)* | |
| R627Q (POLG1) | 18 (7.4%)* | |
| POLG2 | 7 (2.9%)* | |
| other | 60 (24.7%)* | |
| Zygosity | homozygous | 62 (33.7%)* |
| heterozygous compound | 75 (40.7%)* | |
| heterozygous (autosomal dominant variant) | 10 (5.5%)* | |
| n/a | 37 (20.1%)* | |
| Clinical findings | ||
| Ataxia | ||
| gait ataxia | yes | 122 (66.3%) |
| no | 5 (2.7%) | |
| n/a | 57 (31.0%) | |
| dysarthria ± dysphagia | yes | 104 (56.5%) |
| no | 16 (8.7%) | |
| n/a | 64 (34.8%) | |
| limb ataxia | yes | 71 (38.6%) |
| no | 11 (6%) | |
| n/a | 102 (55.4%) | |
| nystagmus | yes | 48 (26.1%) |
| no | 44 (23.9%) | |
| n/a | 92 (50%) | |
| Polyneuropathy | yes | 142 (77.2%) |
| no | 13 (7.1%) | |
| n/a | 29 (15.7%) | |
| CPEO | yes | 114 (62%) |
| no | 53 (28.8%) | |
| n/a | 17 (9.2%) | |
| Epilepsy | yes | 80 (43.5%) |
| no | 69 (37.5%) | |
| n/a | 35 (19%) | |
| Cognitive impairment | yes | 87 (47.3%) |
| no | 63 (34.2%) | |
| n/a | 34 (18.5%) | |
| Psychiatric symptoms | yes | 40 (21.7%) |
| no | 102 (55.4%) | |
| n/a | 42 (22.9%) | |
| Headache | yes | 35 (19%) |
| no | 126 (68.5%) | |
| n/a | 23 (12.4%) | |
| Myoclonus | yes | 55 (29.9%) |
| no | 97 (52.7%) | |
| n/a | 32 (17.4%) | |
| Tremor | yes | 31 (16.8%) |
| no | 112 (60.9%) | |
| n/a | 41 (22.3%) | |
| Outcome/Follow-up | partial improvement** | 4 (2.2%) |
| persistence of symptoms | 14 (7.6%) | |
| loss of independent walking | 6 (3.3%) | |
| wheelchair-bound | 14 (7.6%) | |
| death | 24 (13%) | |
| n/a | 122 (66.3%) |
[i] Abbreviations: CPEO: chronic progressive ophthalmoplegia, *numbers referring to the total number of alleles reported, **partial improvement referring to improvement of certain symptoms such as seizures or movement disorders.
Table 2
Common imaging finding of patients with POLG-related cerebellar ataxia (N = 184).
| IMAGING FINDINGS | ||
|---|---|---|
| Cerebellar atrophy | yes | 58 (31.5%) |
| no | 66 (35.9%) | |
| n/a | 60 (32.6%) | |
| Cerebellar signal changes | yes | 43 (23.4%) |
| no | 76 (41.3%) | |
| n/a | 65 (35.3%) | |
| Cortical changes (atrophy, signal change) | yes | 55 (29.9%) |
| no | 68 (37%) | |
| n/a | 61 (33.1%) | |
| Thalamus signal changes | yes | 29 (15.8%) |
| no | 91 (49.5%) | |
| n/a | 64 (34.7%) | |
| Olivary nucleus signal changes | yes | 18 (9.8%) |
| no | 98 (53.3%) | |
| n/a | 68 (36.9%) | |
| Normal brain MRI | yes | 10 (5.4%) |
| no | 94 (51.1%) | |
| n/a | 80 (43.5%) |
[i] Abbreviations: MRI: magnetic resonance imaging, n/a: not applicable.
Figure 1
Flow chart of studies included in the scoping literature review.
Source: Page MJ, et al. BMJ 2021;372:n71. doi: 10.1136/bmj.n71.
Figure 2
Localization of detected mutations in POLG-protein sequence, most common pathogenic variants can be seen in red color.
Figure 3
Diagnostic flowchart for POLG-related cerebellar ataxia. Differentials can be seen with light gray color. Figure based on initial figure seen by Wong et al. 2018 [46].
Abbreviations: MSA = multiple system atrophy, GAD = glutamic acid decarboxylase, SLE = systematic lupus erythematosus, SCAs = spinocerebellar ataxias, CSF = cerebrospinal fluid, EEG = electroencephalogram, CPEO = chronic progressive ophthalmoplegia.
Figure 4
Diagram showing common symptoms of POLG-related cerebellar ataxia, according to age of onset.