Table 1.
The distribution of the leukodystrophies and genetic leukoencephalopathies based on single gene analysis and WES/panel based gene sequencing in 114 positive patients in the studied population.
| No | Name of disease | Alternative designation, abbreviation | MIM # | Gene | Location of protein | No of families (%) | Genetic testing | Phenotypes | |
|---|---|---|---|---|---|---|---|---|---|
| Single gene | WES | ||||||||
| Leukodystrophies | |||||||||
| 1 | Metachromatic leukodystrophy | MLD | 250100 | ARSA | ER, Lysosome | 19 (16. 7) | 16 | 3 | AG:2, MR:15, DD:2, CI:1, speech problem:6 |
| 2 | Krabbe Disease | KD | 245200 | GALC | Lysosome | 5 (4. 4) | 3 | 2 | Hypotonia:1, speech problem: 2, Spasticity: 2, AG: 2, Seizure: 2, MR: 5, DD:2 |
| 3 | Fucosidosis | 230000 | FUCA1 | Lysosome | 2 (1. 8) | 0 | 2 | Hypotonia:1, Dental germination:1, skin lesions:1, AG:1, DD: 2 | |
| 4 | Salla Disease | SD | 604369 | SLC17A5 | Lysosomal and cell membrane | 1 (0. 9) | 1 | 0 | speech problem, Seizure, DD, MD |
| 5 | Multiple sulfatase deficiency | MSD | 272200 | SUMF1 | ER | 1 (0. 9) | 0 | 1 | dried skin, spasticity, incapable to walk and talk, R, mental retardation, coarse facial feature |
| 6 | RNAse T2 deficiency | 612944 | RNASET2 | ER, Lysosome, Extracellular | 1 (0. 9) | 0 | 1 | Hypotonia, DD | |
| 7 | X-linked adrenoleukodystrophy | X-ALD | 300100 | ABCD1 | Membrane of ER, Mitochondrion, peroxisome and lysosome | 8 (7) | 8 | 0 | Hypotonia: 2, Vision problem: 1, Feeding problem: 2, AG: 3, Seizure: 2, MR: 2, LD:1, CI: 4 |
| 8 | Rhizomelic chondrodysplasia punctata | RCDP | 601757 | PEX7 | Peroxisome | 1 (0. 9) | 0 | 1 | coarse facial feature, cataract, digestive problem, DD, MR |
| 9 | Zellweger Spectrum | ZS | 614883 | PEX13 | Peroxisome membrane | 1 (0. 9) | 0 | 1 | Hypotonia, Seizure, MR, feeding problem |
| 10 | D-bifunctional protein deficiency | DBPD | 601860 | HSD17B4 | Peroxisome | 1 (0. 9) | 0 | 1 | swallowing problem, walking difficulty, speech problem, MR |
| 11 | Canavan Disease | CD | 271900 | ASPA | Nucleus, Cytoplasm | 12 (10. 5) | 12 | 0 | Hypotonia:8, Nystagmus and eye problem:5, Macrocephaly:9, Spasticity:3, Irritable:6, Seizure:3, R: 9, DD:7 |
| 12 | Pelizaeus–Merzbacher-like disease type | PMLD | 260600 | GJC2 | Cell membrane, gap junction | 8 (7) | 6 | 2 | Hypotonia: 6,Nystagmus: 8, Ataxia: 4, Speech problem:6, DD:6 |
| 13 | Megalencephalic leukoencephalopathy with subcortical cysts | MLC | 604004 | MLC1 | ER and cell membrane | 7 (6. 1) | 7 | 0 | Macrocephaly:7, Dystonia: 2, AG: 4, Seizure: 2, MD:2, MR:5 |
| 14 | Vanishing white matter disease | vWM |
606273 603945 606687 |
EIF2B3 EIF2B5 EIF2B4 |
Cytosol Cytosol, nucleus Cytosol |
1 (0. 9) 2 (1. 8) 1 (0. 9) |
0 0 0 |
1 2 1 |
MR:4, Hypotonia: 3,Tremor: 2, AG: 2, Seizure: 2, speech problem 1 |
| 15 | Hypomyelination-hypogonadotropic hypogonadism-hypodontia | 4H |
614366, 614381 |
POLR3A POLR3B |
Nucleus Nucleus |
1 (0. 9) 1 (0. 9) |
0 0 |
1 1 |
Hypotonia: 2, speech problem: 2, Tremor:1, ataxia:2, AG: 2, Seizure:2, MR:1, DD:1, nystagmus:1 |
| 16 | hypomyelination and congenital cataract | HCC | 610532 | FAM126A | Cytosol | 1 (0. 9) | 0 | 1 | congenital cataract |
| 17 | Pelizaeus–Merzbacher disease | PMD | 312080 | PLP1 | Cell (myelin) membrane | 1 (0. 9) | 1 | 0 | MR, Hypotonia, nystagmus |
| 18 | Alexander disease | AxD | 203450 | GFAP | Cytoplasm | 1 (0. 9) | 1 | 0 | Seizure, R, DD, hypotonia |
| 19 | infantile neuroaxonal dystrophy/atypical neuroaxonal dystrophy | INAD | 603604 | PLA2G6 | Peripheral membrane | 1 (0. 9) | 0 | 1 | Hypotonia, bristling head, Seizure |
| 20 | Hypomyelinating leukodystrophy-9 | HLD9 | 616140 | RARS | Cytosol | 1 (0. 9) | 0 | 1 | Spasticity, hypotonia, MD |
| Genetic Leukoencephalopathies | |||||||||
| 21 | Tay-Sachs Disease | TSD | 272800 | HEXA | Lysosome | 11 (9. 6) | 11 | 0 | Vision problem and nystagmus:8, R:6, DD:4 |
| 22 | Sandhoff disease | SHS | 606873 | HEXB | Lysosome | 6 (5. 3) | 5 | 1 | Visual problem:2, Seizure:1, R:4, DD:4 |
| 23 | Gangliosidosis | GM1 | 230500 | GLB1 | Lysosome | 1 (0. 9) | 0 | 1 | |
| 24 | Neuronal Ceroid-Lipofuscinoses | NCL | 204300 |
PPT1, CLN6 |
Extracellular, Lysosome ER membrane |
1 (0. 9) 1 (0. 9) |
0 0 |
1 1 |
Hypotonia:1, speech problem:2, AG: 2, Seizure:2, MR:2, DD:1 |
| 25 | Mucopolysaccharidosis type IIIB | MPS IIIB | 609701 | NAGLU | Lysosome | 1 (0. 9) | 0 | 1 | coarse facial feature, macrocephaly |
| 26 | Cockayne Syndrome | CS | 609413 | ERCC6 | Nucleus | 1 (0. 9) | 0 | 1 | Microcephaly, AG, MR/R |
| 27 | Biotinidase deficiency | BTD | 253260 | BTD | Extracellular | 1 (0. 9) | 1 | 0 | Seizure |
| 28 | L-2-hydroxyglutaric aciduria | L-2-HGA | 236792 | L2HGDH | Mitochondrion | 3 (2. 6) | 2 | 1 | Hypotonia:1, Macrocephaly:1, speech problem: 1, tremor: 1, AG: 1, Seizure: 1, DD: 3, LD:1, Mental retardation:3 |
| 29 | Glutaric acidemia IIC | GAIIC | 231680 | ETFDH | Mitochondrion inner membrane | 1 (0. 9) | 0 | 1 | Walking problem, speech problem, digestive problem, MR |
| 30 | Mitochondrial DNA depletion syndrome 5 | MDDS5 | 612073 | SUCLA2 | Mitochondrion | 1 (0. 9) | 0 | 1 | Dystonia, R, DD |
| 31 | Ataxia neuropathy spectrum | ANS | 203700 | POLG | Mitochondrion | 2 (1. 8) | 0 | 2 | Speech difficulty:1, walking difficulty:1, vision problem:1, ataxia:1, Seizure:1, DD:2 |
| 32 | Leigh syndrome | LS | 185620 | SURF1 | Mitochondrion inner membrane | 3 (2. 6) | 0 | 3 | Muscle weakness:3, walking problem:3, swallowing problem:2, R:3, DD:1 |
| 33 | Mitochondrial complex I deficiency, nuclear type 5 | MC1DN5 | 618226 | NDUFS1 | Mitochondrion inner membrane | 1 (0. 9) | 0 | 1 | Walking problem, Seizure, MR |
| 34 | Mitochondrial complex I deficiency, nuclear type 3 | MC1DN3 | 618224 | NDUFS7 | Mitochondrion | 1 (0. 9) | 0 | 1 | Hypotonia, Seizure |
| 35 | succinate dehydrogenase complex assembly factor 1 deficiency | MCIID | 252011 | SDHAF1 | Mitochondrion | 1 (0. 9) | 0 | 1 | Speech problem, walking problem, R |
| Total | 114 (75) | 74 (49%) | 40 (26%) | ||||||
DD: Developmental delay; LD: learning difficulties; CI: Cognitive impairment; MR/R: Motor regression/retardation; MD: motor delay, MD; AG: Abnormal gait; ER: Endoplasmic reticulum.