Table 1.
Clinical, instrumental and molecular data encountered in 30 unrelated GLD patients
| Neurological findings | Neuroradiologic findings | ||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|
| Pt no. | Sex | Age at onset | Symptoms at onset | Age at exam | Spastidty/ Other signs | MRI findings (WM changes) | CT scan findings (Calcification/WM changes) | NCVs | Sibling♣ | GALC enzymatic activity § (% normal) | GALCGenotype** |
| 1 | F | 1m | Failure to thrive | 7m | +/ Truncal hypotonia | + | ND | Slowed | 4.4 | [c.1161+6532_polyA+9kbdel]+[?] | |
| 2 | F | 3m | Psychomotor regression | 5m | +/ Truncal hypotonia | + (Hypomyel) | ND | Slowed | 8.2 | [p.L469YfsX22]+[p.L469YfsX22]# | |
| 3 | M | 3m | Muscular hypertonia | 6m | +/Nystagmus | + | +/ + | ND | 0.3 | [ p.G553R]+[p.G553R]# | |
| 4 | M | 3m | Irritability, muscular hypertonia | 5m | +/Truncal hypotonia | + | ND | ND | 14.7 | [p.S303F]+[p.G553R] | |
| 5 | M | 3m | Muscular hypertonia. seizures | 6m | +/ Truncal hypotonia | ND | +/ + | ND | yes | 18.5 | [p.E136EfsX35]+[p.E136EfsX35] |
| 6 | F | 3m | Irritability, psychomotor regression | 7m | +/ Truncal hypotonia | + | ND | Slowed | 21.7 | [p.K359AfsX3]+[p.Y567S | |
| 7 | F | 3m | Nystagmus, psychomotor regression | 6m | +/Truncal hypotonia, poor tendon reflexes | + | ND | Slowed | 3.2 | [ p.Y174LfsX3]+[c.1161+6532_polyA+9kbdel] | |
| 8 | M | 4m | Irritability, muscular hypertonia | 6m | +/Nystagmus | + | ND | Slowed | yes | 0 | [p.E130K]+[p.N295T]# |
| 9 | M | 4m | Muscular hypertonia | 6m | +/Truncal hypotonia, poor tendon reflexes | ND | +/ + | ND | 11.1 | [p.H391 IfsX65]+[p.H391 IfsX65] | |
| 10 | M | 4m | Muscular hypertonia | 8m | +/ Truncal hypotonia | ND | -/ + | ND | yes | 5 | [p.T529M]+[c.1161+6532_ polyA+9kbdel] |
| 11 | F | 4m | Muscular hypertonia | 6m | +/ Truncal hypotonia | + (Hypomyel) | ND | Slowed | 8.4 | [p.A21RfsX5]+[p.G553R] | |
| 12 | F | 4m | Irritability, muscular hypertonia | 5m | +/ Truncal hypotonia | + (Hypomyel) | +/ + | ND | yes | 0 | [p.Y314C]+[c.1161+6532_polyA+9kbdel]# |
| 13 | M | 5m | Psychomotor regression | 6m | +/Truncal hypotonia | + | ND | ND | yes | 0 | [ p.F596SfsX1 6] +[p.F596SfsX1 6]# |
| 14 | F | 5m | Psychomotor regression, seizures | 7m | +/ Truncal hypotonia | + (Hypomyel) | ND | Slowed | 0 | [p.G553R]+[p.G553R] | |
| 15 | F | 5m | Irritability, muscular hypertonia | 7m | +/ Truncal hypotonia | + (Hypomyel) | +/ + | ND | 0 | [p.N295T]+[c.1161+6532_polyA+9kbdel] | |
| 16 | F | 5m | Psychomotor regression | 7m | +/ Truncal hypotonia | ND | ND | ND | 8.3 | [p.R127X]+[p.G553R]## | |
| 17 | F | 5m | Muscular hypertonia | 10m | +/ Truncal hypotonia | ND | ND | ND | 4.8 | [p.K88X]+[p.Y490N]# | |
| 18 | M | 5m | Psychomotor regression | 9m | +/ Truncal hypotonia | + | +/ + | ND | 8.8 | [p.R396L]+[c.1161+6532_ polyA+9kbdel] | |
| 19 | M | 5m | Psychomotor regression | 8m | +/ Truncal hypotonia | + | ND | ND | yes | 18.2 | [p.G553R]+[p.G553R]# |
| 20 | M | 5m | Muscular hypertonia | 7m | +/ Truncal hypotonia | + | ND | ND | yes | 9.7 | [p.L634X]+[c.1489+1G>A] |
| 21 | F | 5m | Psychomotor regression | 8m | +/ Truncal hypotonia | + | ND | ND | yes | 0.71 | [p.E130K]+[p.Y490N] |
| 22 | M | 8m | Psychomotor regression | 11m | +/ Truncal hypotonia | + | -/ + | ND | yes | 13.2 | [p.G102GfsX5]+[?] |
| 23 | M | 8m | Psychomotor regression | 11m | +/ Truncal hypotonia | ND | -/ + | ND | yes | 0.26 | [p.D187V]+[p.G323R] |
| 24 | F | 10m | Psychomotor regression | 12m | +/ Truncal hypotonia | + | -/ + | Slowed | yes | 0 | [p.G59R]+[?]# |
| 25 | M | 11m | Irritability, muscular hypertonia | 13m | +/ Truncal hypotonia | ND | -/ + | Slowed | 10.1 | [p.I250T]+[p.R396W] | |
| 26 | F | 3y6m | Gait disturbances and frequent falls | 4y | +/Ataxia, poortendon reflexes | + | ND | Slowed | 5 | [ p.G286D]+[c. 1161 +6532_ polyA+9kbdel]# | |
| 27 | F | 3y6m | Gait disturbances and frequent falls | 3y8m | +/Ataxia | + | -/ + | Normal | NA | [p.R69X]+[p.I384T] | |
| 28 | M | 4y | Gait disturbances and frequent falls | 4y | +/Nystagmus | ND | ND | Slowed | 13 | [p.N295T]+[p.G609GfsX6] | |
| 29 | F | 4y | yReduced visual acuity | 5y9m | +/- | + | -/ + | Normal | yes | 0 | [p.R79H]+[p.G553R] |
| 30 | M | 26y | Gait disturbances and frequent falls | 30y | +/- | + | ND | Slowed | 5 | [p.G286D]+[p.P318R] | |
Legend: Pt=Patient; m= month(s); y=year(s); #Genotype confirmation by parental DNAanalysis; ## only mother's DNAavailable; ND: Not Done; N=Normal; NA: Not Available **GenBank-EMBLaccession no. NM_000153.2 and no. NP_000144.2; Hypomyel= hypomyel inat ion; MRI= Magnetic resonance imaging, WM=white matter; CT= Computed tomography; NCVs= nerve conduction velocity study; ♣ indicates presence of other affected patients in the family; §Owingto the use of different assay met hodsand tissue samples, as reported intheMaterialsand Methods, enzyme act ivity valuesare expressed asa percentage of average control values.