Table 1.
Phenotypes and genotypes of individuals with SLC25A46 pathogenic mutations
| Family ID | Variant studied | Patient, Ref, Country of Origin | SLC25A46 Variants | Age at Symptom Onset | Optic Atrophy | Neurological Features | Neuroimaging | Nerve Conduction Studies |
|---|---|---|---|---|---|---|---|---|
| A | p.R257Q | Current patient (II.2) Turkey |
c.770G>A p.Arg257Gln (homozygous) |
8 months | + | - Hypotonia - Areflexia - Ataxia |
- Brain MRI (5.5y): thickened corpus callosum | Axonal peripheral motor neuropathy (6y) |
| B | p.G249D |
Abrams et al 2015 (1) United Kingdom |
c.165_166insC p.His56fs*94 c.746G>A p.Gly249Asp |
8 years | + | - Lower limb altered sensation and stiffness | - Brain CT and MRI (43y): normal | Axonal motor and sensory polyneuropathy (43y) |
| C | p.R340C |
Abrams et al 2015 (1) Italy |
c.1018C>T p.Arg340Cys (homozygous) |
2 years | + | - Ataxia and stepping gait - Severe lower limb hypotrophy - Pes cavus |
- Brain MRI (28y): diffuse brain and cerebellar atrophy, cerebellar white matter changes, marked chiasm atrophy - CT brain (44y): small calcifications of the basal ganglia |
Axonal sensorimotor polyneuropathy (18y) |
| D | p.E335D |
Abrams et al 2015 (1) Palestine |
c.1005A>T p.Glu335Asp (homozygous) |
1–2 years | + | - Gross and fine motor delay - Hypertonia - Hyper-reflexia - Ataxia |
- Brain MRI (22m): prominent extra-axial spaces - Brain MRI (5.2y): bilateral cerebellar encephalomalacia with increased gliosis signal - Brain MRI (11.5y): brainstem and cerebral volume loss |
Absent motor responses (excluding the right median nerve) (5y) |
| E | p.P333L |
Abrams et al 2015 (1) United States |
c.882_885dupTTAC p.Asn296fs*297 c.998C>T p.Pro333Leu |
Birth (deceased at 15 weeks) |
+ | - Hypotonia - Congenital contractures |
- Brain MRI (neonate): moderate cerebellar atrophy, mild brainstem atrophy - Brain MRI (3m): severe atrophy of cerebellar hemispheres and brainstem, diffuse volume loss |
Generalised neuropathy (3m) |
| F |
Nguyen et al 2017 (2) Morocco |
c.283+3G>T p.Ser32Thrfs*4 (homozygous) |
Birth (deceased at 7 days) |
+ | - Hypotonia - Myoclonic jerks |
- Brain MRI (neonate): atrophic cerebellar hemispheres, retrocerebellar arachnoid cyst, diffuse atrophy | Not tested | |
| G | p.T142I |
Janer et al 2016 (3) French Canadian |
c.425C>T p.Thr142Ile (homozygous) |
4 months (deceased at 13.5 months) |
Pale optic discs | - Psycho-motor delay - Hypertonia/spasticity |
- Brain MRI (13.5m): lesions in the cerebellar hemispheres, periaqueductal grey matter, brainstem and midbrain | Not tested Muscle biopsy: neurogenic atrophy, no ragged red fibres |
| H | p.L138R |
Charlesworth et al 2016 (4) Pakistan |
c.413T>G p.Leu138Arg (homozygous) |
Infancy | + | - Poor balance in infancy - Myoclonus (generalised, action induced, stimulus sensitive) - Cerebellar ataxia - Nystagmus, dysmetria, tremor |
- Brain MRI: cerebellar atrophy as well as T2/FLAIR (fluid-attenuated inversion recovery) hyperintensities and cavitations in the cerebellum | Axonal sensory-motor neuropathy leading to trophic changes |
| I |
Wan et al 2016 (5) Country of origin not specified |
c.1022T>C p.Leu341Pro (homozygous) |
Birth (died at 4 weeks of age) |
+ | - Myoclonic jerks - Flexion contractures (knees, elbows) |
- Brain MRI (5d): small cerebellum and brainstem | Severe axonal sensorimotor neuropathy |
|
| J |
Wan et al 2016 (5) Country of origin not specified |
5q22.1 (110738771–110740670) hmz del | Birth (died at 6 weeks of age) |
+ | - Hypotonia - Areflexia - Myoclonic jerks (occasional) |
- Brain MRI: pontocerebellar hypoplasia | Not tested |