Genotype |
p.L628Q |
p.A232fsX64 |
p.A232fsX64 |
p.R518Q |
p.S358X |
p.A401W |
p.P560L |
p.P426L/p.P426L; PD negative at ARSA gene |
p.P426L/ p.P426L; PD negative at ARSA gene |
p.W402X/ p.W402X |
p.W402X/ p.W402X |
Age at onset of cerebral signs (years) |
8.9 Addison-only at 7yo |
18 |
6.5 |
9.5 Addison-only at 7yo |
7.5 |
6.4 |
27.5 |
NA |
19 |
0.8 |
0.9 |
Age at HSCT (years) |
9.4 |
19.4 |
8 |
10.9 |
8.4 |
6.5 |
28.2 |
9.1 |
20.6 |
2.1 |
1.9 (first HSCT) and 2.8 (second HSCT) |
Neurological and clinical examination findings at the time of HSCT |
Asymptomatic |
AMN without encephalic manifestations |
Ataxia, ankle clonus and attention deficit to auditory stimuli |
Asymptomatic |
Asymptomatic |
Brisk reflexes on the left hemibody |
Hemiparesis, dysarthria and a conduction aphasia |
Intermittent strabismus |
Personality changes, seizures and cognitive loss. Babinski sign on right side |
Recurrent upper air infections, hepatomegaly, failure to thrive, developmental delay, and coarse facies. Severe PMD retardation: unable to walk or talk. |
Moderate PMD retardation: at the time of first HSCT, still starting to walk and talk. |
Age and status at last follow-up (time elapsed) |
16yo (7 years after HSCT): No complains Mild signs of neuropathy on neurological examination |
27yo (8 years and 9 months after HSCT) ): AMN without encephalic manifestations. Progressive worsening of gait since 18yo (needs canes for walking since 25yo). |
9yo (12 months after HSCT) Severe GVHD. Marked worsening: aphasia, tetraparesis |
16yo (5 years after HSCT): Stable (clinically normal). NCS disclosed peripheral neuropathy. |
13y10m (5 years after HSCT): Stable (asymptomatic) |
8y8m (2 years after HSCT): Stable (brisk reflexes on the left hemibody) |
29yo (9 months after HSCT): Death due to Chronic GVH + opportunistic infection 9 months after HSCT |
16yo (7 years and 6 months after HSCT) Stable. Normal neurological examination. Focal seizures controlled with valproic acid. Subclinical demyelinating polyneuropathy on nerve conduction studies, and slowed P40 latencies at somatosensory evoked responses. Normal visual evoked responses. |
22 yo (18 months after HSCT) Akinetic mutism |
5y11m (3 years and 8months after HSCT) Stable. No further cognitive losses, Communication was nonverbal, though enough to her daily needs. Coarse facies, weight and height on percentile 3, gibbosity, and joint restriction in hands, arms and legs still present. No hepatomegaly on ultrasound. Thickening of the leaflets of the aortic and mitral valves without changes in transvalvular flow on echocardiogram. |
3 years: Death due opportunistic infection at 23 days after 2nd HSCT |
Baseline IQ |
Performance 103 Total 96 |
Performance 105 Total 91 |
NA |
Performance 141 Total 140 |
Performance 99 Total 86 |
NA |
NA |
NA |
NA |
NA |
NA |
Last IQ (time elapsed) |
Performance 106 Total 105 (5 years later) |
NA |
NA |
Performance 136 Total 123 (2 years later) |
Performance 108 Total 105 (2 years later) |
NA |
NA |
NA |
NA |
NA |
NA |
Baseline MRI: (CALD-Loes score, MLD-Eichler score) |
Loes of 2 |
Loes of 6.5 |
Loes of 4.5 |
Loes of 4.5 |
Loes of 4 |
Loes of 3 |
Loes of 8 |
Eichler score of 10 |
Eichler score of 20 |
WM lesions in the periventricular and deep WM associated with mild ventricular enlargement (Figure 4A-B) |
----- |
Last MRI: (CALD-Loes score, MLD-Eichler score) |
Loes of 1 (7y after HSCT) |
Loes of 4 (6 years and 9 months after HSCT) |
Loes of 7 (12 months after HSCT) |
Loes of 6.5 (5 years and 6 monts after HSCT) |
Loes of 4 (5 years after HSCT) |
Loes of 7 (2 years after HSCT) |
Loes of 8 (2 months after HSCT) |
Eichler score of 12 (5 years after HSCT) |
NA |
Significant reduction of periventricular and deep WM lesions. Mild ventricular enlargement also improved (Figure 4C and D) (3 years after HSCT) |
NA |
Baseline biochemical markers |
C26: 2.2 µmol/L C26/22 ratio 0.04 |
C26:3.47 µmol/L C26/22 ratio 0.10 |
C26:2.90 µmol/L C26/22 ratio 0.15 |
C26: 1.94 µmol/L C26/22 ratio 0.06 |
C26: 4.33 µmol/L C26/22 ratio 0.049 |
C26: 3.54 µmol/L C26/22 ratio 0.08 |
C26: 4.53 µmol/L C26/22 ratio 0.07 |
ARSA activity in leukocytes: 1 nmol/h/mg prot Urinary sulfatides ++ |
ARSA activity in leukocytes: undetectable Urinary sulfatides: ++ |
α-L-iduronidase activity in leukocytes: 0.2 nmol/h/mg prot Urinary GAGs: 532 ug/mg creatinine |
α-L- iduronidase activity in leukocytes: 4.0 nmol/h/mg prot Urinary GAGs: 638 ug/mg creatinine |
Last biochemical markers(time elapsed) |
C26:2.9 µmol/L C26/22 ratio 0.05 ( 6 years) |
NA |
C26:5.7 µmol/L C26/22 ratio 0.16 (1 month) |
C26:1.9 µmol/L C26/22 ratio 0.13 (6 years) |
C26: 1.8 µmol/L C26/22 ratio 0.17 (5 years) |
C26: 0.7 µmol/L C26/22 ratio 0.12 (2 years) |
NA |
ARSA activity in leukocytes: 9.5 ml/mg of prot/h Urinary sulfatides ++ (6 years) |
ARSA activity in leukocytes: 5.3 nmol/h/mg prot |
α-L- iduronidase activity in leukocytes: 22 nmol/h/mg prot Urinary GAGs:185 ug/mg creatinine |
α-L- iduronidase activity in leukocytes: 12 nmol/h/mg prot Urinary GAGs:289 ug/mg creatinine |