Table 2 Overview of reported FARS2 deficiency subjects [2,3,4,5,6,7,8,9,10,11,12,13,14,15,16,17,18,19,20,21,22,23]
Subject | Mutations | Gender | Onset age (outcome) | Ethnicity | Consanguinity | Developmental delay | Elevated lactate | Seizure | MRI findings | References |
|---|---|---|---|---|---|---|---|---|---|---|
Early-onset epileptic encephalopathy | ||||||||||
1 | c.431A > G (p.Y144C) | F | 35 days (died at 20 months) | Arab | Yes | Yes | Yes | Uncontrolled myoclonic epilepsy | Cortical atrophy, widened sulci and fluid accumulation (at 1.5 years) | [2] |
2 | c.431A > G (p.Y144C) | M | NA (died before 3 months) | Arab | Yes | Yes | NA | Uncontrolled myoclonic epilepsy | NA | [2] |
3 | c.431A > G (p.Y144C) | M | NA (died before 3 months) | Arab | Yes | Yes | NA | Uncontrolled myoclonic epilepsy | NA | [2] |
4 | c.986 T > C (p.I329T), c.1172A > T (p.D391V) | F | 2 days (died at 8 months) | Finnish | Yes | Yes | Yes | Myoclonic epilepsy, Multifocal seizures, Refractory | Normal at 4 days, extensive cortical atrophy with slight bilateral signal increase in the putamina at 3 months | [3] |
5 | c.986 T > C (p.I329T), c.1172A > T (p.D391V) | F | 4 days (died at 21 months) | Finnish | Yes | Yes | NA | Refractory | NA | [3] |
6 | c.973G > T (p.D325Y), chr 6p25.1 del | M | 6 months (alive at 30 months) | British | No | Yes | NA | Infantile spasms, focal seizures | Symmetrical subcortical white matter lesions. Thinning of corpus callosum | [4] |
7 | c.1156C > G (p.R386G) chr6: del | M | 3 months (alive at 3 years) | Romanian | No | Yes | Yes | Infantile spasms (3 months), Seizure free (20 months) | severe brain atrophy, hyperintensity of T2 signal abnormalities in hemispheric white matter and dentate nuclei, thin corpus callosum | [5] |
8 | c.925G > A (p.G309S) | M | 3 months (alive at 3 years) | Korean | No | Yes | Yes | GTC, SE, myoclonic | diffuse brain atrophy at 3 months; Progression of atrophic changes and myelination delay at 6 months | [6] |
9 | c.925G > A (p.G309S) | F | 4 months (alive at 17 months) | Korean | No | Yes | No | Myoclonic at right hand, GTC, SE | Thin corpus callosum and generalized brain atrophy | [6] |
10 | c.925G > A (p.G309S) | M | 4 months (died at 8 months) | Korean | No | Yes | Yes | Infantile spasms, SE | Mild brain atrophy | [6] |
11 | c.925G > A (p.G309S) | F | 3 months (died at 44 months) | Korean | No | Yes | Yes | GTC, focal clonic | Mild brain atrophy | [6] |
12 | c.431A > G (p.Y144C) | F | 4 months (died at 23 months) | Arab | Yes | Yes | Yes | Seizures of unknown type | Brain atrophy, thin corpus callosum | [7] |
13 | c.431A > G (p.Y144C) | F | 40 days (died at 3 months) | Arab | Yes | Yes | Yes | Seizures of unknown type | Brain atrophy | [7] |
14 | c.431A > G (p.Y144C) | M | 1 month (alive at 2 years) | Arab | Yes | Yes | Yes | Seizures of unknown type | Brain atrophy, thin corpus callosum | [7] |
15 | c.431A > G (p.Y144C) | F | 2 months (NA) | Arab | NA | Yes | Yes | Seizures of unknown type | NA | [7] |
16 | c.431A > G (p.Y144C) | F | 1 month (alive at 1 years) | Arab | No | Yes | Yes | Seizures of unknown type | Brain atrophy, thin corpus callosum | [7] |
17 | c.431A > G (p.Y144C) | M | 1 month (died at 3 months) | Arab | Yes | Yes | Yes | Seizures of unknown type | thin corpus callosum | [7] |
18 | c.431A > G (p.Y144C) | F | 1 month (alive at 13 months) | Arab | No | Yes | Yes | Seizures of unknown type | Brain atrophy, thin corpus callosum | [7] |
19 | c.431A > G (p.Y144C) | F | 5 month (died at 2 years) | Arab | Yes | Yes | Yes | Seizures of unknown type | Brain atrophy, thin corpus callosum | [7] |
20 | c.431A > G (p.Y144C) | F | 1 month (alive at 4.5 months) | Arab | Yes | Yes | Yes | Seizures of unknown type | Brain atrophy, thin corpus callosum | [7] |
21 | c.431A > G (p.Y144C) | F | 20 days (died at 4 months) | Arab | Yes | Yes | Yes | Seizures of unknown type | Brain atrophy, thin corpus callosum | [7] |
22 | c.431A > G (p.Y144C) | F | 25 days (died at 3.5 months) | Arab | Yes | Yes | Yes | Seizures of unknown type | Brain atrophy, thin corpus callosum | [7] |
23 | c.667C > T (p.R223C) | M | 6 weeks (died at 10 months) | NA | Yes | Yes | Yes | multifocal clonic seizures and erratic myoclonic fits | NA | [8] |
24 | c.925G > A (p.G309S) | 3 months (NA) | Korean | NA | Yes | NA | Seizures of unknown type | NA | [9] | |
25 | c.989G > A (p.R330H), c.1113G > T (p.L371P) | F | 6 weeks (alive at 16 years) | French | No | Yes | Yes | myoclonic focal and generalized seizures, refractory | Marked ventriculomegaly, abnormal T2 hyperintensities in the lentiform nuclei and dorsal brainstem | [10] |
26 | c.1256G > A (p.R419H), c.251A > C (p.H84P) | M | 10 months (alive at 5 years) | French | No | Yes | Yes | Myoclonic generalized and focal seizures | Variably severe ventriculomegaly, Dentate nuclei, brainstem, and pallidal T2 hyperintensity | [10] |
27 | c.925G > A (p.G309S), c.943G > C (p.G315R) | M | 1 day (died at 37 days) | Chinese | No | Yes | Yes | No epileptic seizures | cortical thinning, long T1 and long T2 signal shadows in the bilateral external capsule, enlargement of the ventricles | [11] |
28 | c.925G > A (p.G309S), c.943G > C (p.G315R) | F | 1 day (died at 34 days) | Chinese | No | Yes | Yes | No epileptic seizures | Unclear corticomedullary demarcation of the bilateral cerebral hemispheres, enlargement of the ventricles, widened cerebral sulci and fissure | [11] |
29 | c.925G > A (p.G309S), c.550G > T (p.D184Y), | F | 1 day (died at 2 months) | Chinese | NA | Yes | Yes | No epileptic seizures | NA | [22] |
30 | c.424G > T (p.D142Y), c.988C > T (p.R330C) | NA | NA | Chinese | NA | NA | NA | Generalized or secondary generalized tonic–clonic seizures, epileptic spasms, focal seizures, refractory | NA | [23] |
31 | c.479A > G (p.Q160R), c.727C > T (p.L243F) | NA | NA | Chinese | NA | NA | NA | Epileptic spasms, refractory | NA | [23] |
Hereditary spastic paraplegia | ||||||||||
32 | c.476 A > C (p.H159P), c.1255 C > T (p.R419C) | F | 2 year (alive at 20 years) | North American | No | Yes | No | No epileptic seizures | Brain atrophy | [4] |
33 | c.476 A > C (p.H159P), c.1255 C > T (p.R419C) | F | 1 year (alive at 17 years) | North American | No | Yes | No | No epileptic seizures | NA | [4] |
34 | c.1256G > A (p.R419H), 1269-76dup (p.S426*) | F | 1 month (alive at 8 years) | French and Chinese | No | Yes | Yes | No epileptic seizures | mild ventriculomegaly | [10] |
35 | c.1255C > T (p.R419C), chr 6p21 del | F | 2 months (alive at 5.5 years) | mixed European ancestry | NA | Yes | Yes | One seizure at 2 months of age after receiving vaccinations | Normal at 3 years | [12] |
36 | c.1255C > T (p.R419C), chr 6p25.1 del | M | 6 weeks (alive at 14 years) | mixed European ancestry | NA | Yes | NA | several seizures before 6 weeks, no recurrence | Two small foci of T2/FLAIR signal in periventricular and deep white matter of right posterior frontal lobe at 13 years | [12] |
37 | c.424G > T (p.D142Y) | F | 2 year (alive at 41 years) | Chinese | Yes | No | No | No epileptic seizures | Normal | [13] |
38 | c.424G > T (p.D142Y) | M | 1 year (alive at 30 years) | Chinese | Yes | No | No | No epileptic seizures | Normal | [13] |
39 | c.424G > T (p.D142Y) | F | 5 year (alive at 26 years) | Chinese | Yes | No | No | No epileptic seizures | Normal | [13] |
40 | c.424G > T (p.D142Y) | F | 3 year (alive at 23 years) | Chinese | Yes | No | No | No epileptic seizures | Normal | [13] |
41 | c.461 C > T (p.A154V), c.1082 C > T (p.P361L) | M | 6 months (alive at 19 years) | NA | No | Yes | Yes | Mild seizures only between 15 and 30 months of age | Signal abnormalities in anterior parts of mesencephalon Diffuse brain atrophy | [14] |
42 | c.521_523del (p.V174del), c.1082 C > T (p.P361L) | F | 10 months (alive at 15 years) | NA | NA | Yes | Yes | No epileptic seizures | Signal abnormalities in tegmentum and periaqueductal grey matter Mild progressive cerebellar atrophy | [14] |
43 | c.646 C > T (p.Q216*) c.407 C > A (p.P136H) | M | 2.5 year (alive at 9 years) | Northern European and Ashkenazi Jewish | No | No | NA | No epileptic seizures | Abnormal signal hyperintensities in the bilateral dentate nuclei | [15] |
44 | c.422G > A (p.G141E) chr6: del | M | 18 months (alive at 13 years) | Irish | No | NA | NA | No epileptic seizures | Normal | [16] |
45 | c.422G > A (p.G141E) chr6: del | F | 24 months (alive at 7 years) | Irish | No | NA | NA | No epileptic seizures | Normal | [16] |
46 | p. D364G | F | NA (alive at 9 years) | NA | NA | NA | NA | NA | NA | [17] |
47 | c.1082 C > T (p.P361L) ex. 1–2 del | M | 5 year (alive at 22 years) | Czech Roma | No | No | NA | No epileptic seizures | Normal | [18] |
Juvenile-onset epilepsy | ||||||||||
48 | c.253C > G (p.P85A) c.403 C > G (p.H135D) | F | 8 years (died at 15 years) | NA | No | Yes | No | GTC, SE, focal seizures, progressive myoclonus | Extensive signal abnormalities in left caudate, cortex and cerebellum | [19] |
49 | c.589G > A (p.V197M) c.1205 T > C (p.F402S) | M | 12 years (died at 20 years) | Chinese | No | No | Yes | generalized, partial and/or secondary generalized convulsive status epilepticus | Increased wandering lesions involving bilateral frontal, temporal, and parietal lobes, occipital cortex and subcortical | [20] |
50 | c.589G > A (p.V197M) microdeletion | F | 16 years (alive at 17 years) | NA | No | No | No | super refractory focal motor status epilepticus | Restricted diffusion in the cortical-subcortical areas of the right frontal lobe, right insula, right thalamus and to lesser extent in the right temporal, both parietal lobes and left frontal lobe | [21] |
Onset or phenotype unknown | ||||||||||
51 | c.1275G.C (p.L425L), c.1277C.T (p.S426F) | NA | NA | NA | NA | NA | NA | NA | NA | [3] |
52 | c.431A > G (p.Y144C) c.530 T > A (p.V177D) | F | died at 2 days | Arab | Yes | NA | Yes | No | NA | [7] |
53 | c.925G > A (p.G309S) c.457A > G (p.R153G) | F | NA | Hispanic | NA | NA | Yes | NA | NA | [7] |
54 | c.467 C > T (p.T156M) c.905-1G > A (splice-acceptor) | F | NA | NA | NA | NA | NA | NA | Epileptic encephalopathy | [25] |
55 | c.467 C > T (p.T156M) intragenic deletion | NA | NA | NA | NA | NA | Yes | NA | Signal abnormalities in dentate nuclei | [26] |
56 | c.989G > A (p.R330H), c.1113G > T (p.L371P) | NA | NA | NA | NA | NA | Yes | NA | Signal abnormalities in putamen, dentate nuclei | [26] |
57 | c.1256G > A (p.R419H), c.251A > C (p.H84P) | NA | NA | NA | NA | NA | Yes | NA | Signal abnormalities in caudate nuclei, putamen, dentate nuclei | [26] |
58 | c.1256G > A (p.R419H), 1268-69ins (p.T424*) | NA | NA | NA | NA | NA | Yes | NA | NA | [26] |