Table 2.
Summary of demographic and clinical data.
| # | Disorder/Total | Gene | Number of patients | M:F | Age of onset (yrs) | Age of diagnosis (yrs) | Current age (years) | Neuroregression | Global developmental delay | Seizure | Type of seizure | MRI findings | Long term outcome |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| 1 | Metachromatic leukodystrophy (MLD) (21) | ARSA | 11 | 5:6 | 0.8-1.5 | 2–4 | 6–11 | 11/11 | 11/11 | 6/11 | GTC, IS | Supratentorial deep periventricular white matter abnormal signal with the sparing of the subcortical U fibers. | 7 deceased and 4 alive with severe GDD |
| PSAP | 10 | 8:2 | 1.5–3 | 2.5–8 | 5–12 | 09/10 | 10/10 | 2/10 | GTC | Diffuse bilateral cerebral subcortical and deep white matter T2/FLAIR hyperintensity sparing the subcortical U-fibers, involving the posterior limbs of the internal capsules and middle cerebellar peduncles. | Alive with severe GDD | ||
| 2 | Leukoencephalopathy with vanishing white matter (11) (VWM) | EIF2B4 | 7 | 5:2 | 0.9–2 | 0.4–3 | 2–6 | 4/7 | 7/7 | 5/7 | GTC | Diffuse white matter T2 high signal intensity with significant delay myelination for the patient's age. | 5 deceased and 2 alive |
| EIF2B2 | 2 | 1:1 | 2 | 3.5 | 8 | 2/2 | 2/2 | 0/2 | 0/2 | Bilateral supratentorial confluent white matter increased signal intensity sparing the juxtracortical white matter with multiple areas of linear and dot-like white matter | Alive with severe developmental delay | ||
| EIF2B3 | 2 | 0:2 | 0.6–2 | 3 | 7,9 | 2/2 | 4/4 | 4/4 | Focal | Diffuse bilateral periventricular and deep white matter T2 high signal intensity extending into the subcortical region. It shows diffuse low signal intensity on T1 weighted | Alive with severe developmental delay | ||
| 3 | Peroxisome biogenesis disorders (PBD) (10) | PEX1 | 4 | 2:2 | 0–0.3 | 0–0.2 | 0.3–0.6 | 0/4 | 4/4 | 3/4 | Focal | Focal abnormal signal intensity seen at the posterior left putamen / external capsule which shows high signal intensity on T2 /FLAIR sequence with diffusion restriction, most likely hypoxo-ischemic foci. | All deceased |
| HSD17B4 | 3 | 2:1 | 0–0.2 | 0–0.6 | 0.6–0.8 | 0/3 | 3/3 | 2/3 | Focal | Hyperintensity in the peritrigonal whitematter on both sides with splenium involvement of the corpus callosum | 2 alive and 1 died | ||
| PEX13 | 1 | 1:0 | 0 | 0.3 | 0.3 | 0 | 1 | 1 | Focal | Peritrigonal white matter disease and thinning corpus callosum | Deceased | ||
| PEX16 | 1 | 0:1 | 0 | 5 | 6 | 1 | 1 | 0 | 0 | White matter disease and thinning corpus callosum | Alive with severe developmental delay | ||
| PEX6 | 1 | 1:0 | 1 | 1.5 | 3.3 | 0 | 1 | 1 | Focal | White matter disease and | Alive with severe developmental delay | ||
| 4 | Aicardi Goutieres syndrome (AGS) (9) | RNASEH2B | 3 | 2:1 | 0–1 | 1–4 | 3–7 | 0/3 | 3/3 | 2/3 | Myoclonic | Local areas of hyperintensity on T1W images with corresponding hypointensities on T2W images are observed bilaterally within the basal ganglia and periventricular white matter bilaterally consistent with distribution seen on CT scan suggestive of calcific foci. Preventricular leukomalacia, CNS calcification. | Alive |
| RNASEH2A | 2 | 1:1 | 0–1 | 1,2 | 5 | 0/2 | 2/2 | 0/2 | 0/2 | Multifocal T2 high signal intensity. | Alive | ||
| RNASEH2C | 1 | 1:0 | 0.1 | 0.7 | 3 | 0/1 | 1/1 | 1/1 | GTC | Interval progression of lost white matter bulk with atrophic changes seen in allover supra and infra tentorial structures with prominent CSF spaces and ventricles. No changes regarding focal calcification in pons with development of bilateral basal ganglia. | Alive | ||
| IFIH1 | 1 | 0:1 | 0.8 | 3 | 4 | 1/1 | 1/1 | 0/1 | 0/1 | Abnormal white matter distribution. | Alive | ||
| SAMHD1 | 1 | 1:0 | 0 | 0.3 | 1 | 0/1 | 1/1 | 1/1 | GTC | Multiple patchy areas of high signal intensity on T2-weighted and FLAIR sequences. | Alive | ||
| TREX1 | 1 | 0:1 | 4 | 5 | 5.5 | 0 | 0/1 | 0 | 0 | Abnormal diffused white matter. | Alive | ||
| 5 | Krabbe Disease (7) | GALC | 7 | 4:3 | 0.3–4 | 1–5 | 5–12 | 6/6 | 6/6 | 3/6 | Clonic, myoclonic | Bilateral diffuse symmetrical T2 abnormal high signal intensity involving the deep white matter with sparing of the immediate subcortical white matter. It extends from the centrum semiovale, corona radiata, periventricular white matter and involving the posterior limb of the internal capsule. Diffusion-weighted images show no evidence of diffusion restriction. | 2 deceased and 4 alive |
| 6 | Pelizaeus-Merzbacher-Like Disease (6) | GJC2 | 6 | 3:3 | 0–0.6 | 0.3–3 | 4–10 | 0/6 | 6/6 | 0/6 | 0/6 | Extensive bilateral diffuse T2 hyperintensity of the white matter with relative sparing of the subcortical white matter in the temporal lobe. Involvement of the pons and middle cerebral peduncle is noted. | Alive with severe developmental delay |
| 7 | Megalencephalic Leukoencephalopathy with subcortical cyst (MLC) (5) | MLC1 | 4 | 2:2 | 2–7 | 1–19 | 7–25 | 0/4 | 1/4 | 2/4 | GTC | Bilateral symmetric abnormal white matter cerebellar and cerebellum signal on T1 and T2. Early subcortical cystic changes are seen in the anterior temporal lobes bilateral. | Alive with severe developmental delay |
| HEPACAM | 1 | 1:0 | 0.7 | 7 | 15 | 0/1 | 1/1 | 1/1 | Focal | Diffuse supratentorial superficial and deep white matter disease with relative sparing of the basal ganglia. There is partial involvement of the dorsal brainstem tracts. There is involvement of the deep cerebellar white matter and dented nuclei. Small subcortical. | Alive with severe developmental delay | ||
| 8 | Canavan disease (4) | ASPA | 4 | 4:0 | 0–1 | 0.5–2 | 2–6 | 1/4 | 4/4 | 1/4 | GTC | Extensive diffuse bilateral low T1, high T2 white matter hyperintensity with modified restricted diffusion involving subarcuate U fibers, bilateral globi pallidi, thalami, brain stem and cerebellum is observed. | Alive |
| 9 | X-Linked Adrenoleukodystrophy (3) | ABCD1 | 3 | 3:0 | 4–5 | 5–6 | 7–8 | 3/3 | 3/3 | 3/3 | Focal | Extensive symmetrical white matter changes in the parieto-occipital region on axial FLAIR sequence. Post gadolinium contrast T1 weighted images shows peripheral enhancement | All alive with severe developmental delay |
| 10 | Alexander Disease (2) | GFAP | 2 | 1:1 | 0.3,2 | 0.4,7 | 0.4, 8 | 0/0 | 1/1 | 2/2 | Focal, GTC | Bilateral diffuse symmetrical white matter signal abnormalities predominantly involving the frontal and anterior parietal lobes | Alive |
| 11 | Pelizaeus-Merzbacher disease (PMD) (2) | PLP1 | 2 | 2:0 | 0.5–1 | 1–3 | 5–7 | 0/2 | 2/2 | 0/2 | 0/2 | Abnormal CNS demyelination | Alive with severe developmental delay |
| 12 | Salla disease (2) | SLC17A5 | 2 | 1:1 | 0.8–1 | 4–5 | 7–9 | 0/2 | 2/2 | 1/2 | Myoclonic | Diffuse supratentorial abnormal signal involving the superficial and deep white matter. There is relative sparing of the cortex and deep gray matter and hypomyelination | Alive with severe developmental delay |
| 13 | Oculodentodigital dysplasia (1) | GJA1 | 1 | 0:1 | 0.1 | 6 | 7 | 0/1 | 1/1 | 0/1 | 0 | Scattered small foci of hyperdensities in right subcortical frontal region and frontparietal region likely calcifications with high attenuation of the basal ganglia. No white matter changes noted | Alive with mild mental retardation |