Clinical characteristics of patients with ALDH18A1 mutations: autosomal recessive families
| Family N°/Origin . | FSP856/Spain . | SR45/Portugal . | ||||
|---|---|---|---|---|---|---|
| ALDH18A1 variant/Inheritance | p.Asp715His, p.Asp715His/Recessive | p.Arg128His, p.Leu637Pro/Recessive | ||||
| Individual N° (sex) | 18 (M) | 19 (M) | II:3 (F) | II:4 (F) | II:6 (M) | II:9 (F) |
| Age at exam (years) | 42 | 39 | 44 | 49 | 46 | 43 |
| Age at onset (Years) | 7 | 7 | <1 | <1 | <1 | <1 |
| Symptoms at onset | Toe walking, ID, speech delay | ID, gait difficulties | MD, growth retardation | MD, growth retardation | PMD | Severe MD, growth retardation |
| Disease duration (years) | 35 | 32 | 44 | 49 | 46 | 43 |
| Disability score (max 7) | 6/7 | 3/7 | 7/7 | 7/7 | 6/7 | 7/7 |
| Spasticity at gait | Severe | Moderate | Severe, ambulation lost at 30 | Severe | Severe, ambulation lost at 15 | Severe, no ambulation |
| Spasticity at rest | Severe | Moderate | Severe Ashworth 4/4 | Severe Ashworth 3/4 UL; 4/4 LL | Severe Ashworth 4/4 LL; 2/4 UL | Severe Ashworth 4/4 |
| Weakness | Proximal, distal | No | Tetraplegia, drop-feet | Tetraparesia, drop-feet | MRC grading LL 0/5, UL 4/5 | Tetraplegia |
| Increased reflexes LL | Yes | Yes | Yes (ankles abolished) | Yes (ankles abolished) | Yes (ankles abolished) | Not awakened |
| Increased reflexes UL | Yes | Yes | Yes | Yes | Yes | Not awakened |
| Extensor plantar response | Yes | Yes | Yes | Yes | Yes | Indifferent |
| Hoffman sign | NA | NA | NA | NA | NA | NA |
| Decreased vibration sense at ankles | Mild | Mild | NA | NA | No | NA |
| Urinary symptoms | Urinary retention, pollakiuria | No | Incontinence | Incontinence | Incontinence | Incontinence |
| Cerebellar gait | NA | No | No | No | No | NA |
| Cerebellar signs UL | Postural tremor | Postural tremor | No | No | No | NA |
| Dysarthria | No | No | Pseudobulbar, loss of speech (age 30) | Pseudobulbar | Spastic | No speech ever |
| Cognitive impairment | Intellectual deficit IQ 49 | Intellectual deficit IQ 35‐50 | ID, progressive deterioration | ID, progressive deterioration | ID, progressive deterioration | Profound |
| Cutaneous findings | No | No | No | No | No | No |
| Ocular findings | NA | NA | NA | NA | Probable cataract (on neurological examination) | NA |
| Other clinical features | Microcephaly (HC 52 cm, −2 SD), facial dysmorphy | Microcephaly (HC 52 cm, −2 SD), facial dysmorphy | Microcephaly, growth retardation, facial dysmorphy; generalized muscle atrophy | Microcephaly, short stature, generalized muscle atrophy | Mild facial dysmorphy, distal amyotrophy (UL, LL) | Severe growth retardation, cyphoscoliosis, archaic reflexes, extreme muscle atrophy |
| MRI | Normal brain MRI | NA | NA | NA | CC atrophy, periventricular white matter anomalies, mild cortical atrophy | NA |
| Family N°/Origin . | FSP856/Spain . | SR45/Portugal . | ||||
|---|---|---|---|---|---|---|
| ALDH18A1 variant/Inheritance | p.Asp715His, p.Asp715His/Recessive | p.Arg128His, p.Leu637Pro/Recessive | ||||
| Individual N° (sex) | 18 (M) | 19 (M) | II:3 (F) | II:4 (F) | II:6 (M) | II:9 (F) |
| Age at exam (years) | 42 | 39 | 44 | 49 | 46 | 43 |
| Age at onset (Years) | 7 | 7 | <1 | <1 | <1 | <1 |
| Symptoms at onset | Toe walking, ID, speech delay | ID, gait difficulties | MD, growth retardation | MD, growth retardation | PMD | Severe MD, growth retardation |
| Disease duration (years) | 35 | 32 | 44 | 49 | 46 | 43 |
| Disability score (max 7) | 6/7 | 3/7 | 7/7 | 7/7 | 6/7 | 7/7 |
| Spasticity at gait | Severe | Moderate | Severe, ambulation lost at 30 | Severe | Severe, ambulation lost at 15 | Severe, no ambulation |
| Spasticity at rest | Severe | Moderate | Severe Ashworth 4/4 | Severe Ashworth 3/4 UL; 4/4 LL | Severe Ashworth 4/4 LL; 2/4 UL | Severe Ashworth 4/4 |
| Weakness | Proximal, distal | No | Tetraplegia, drop-feet | Tetraparesia, drop-feet | MRC grading LL 0/5, UL 4/5 | Tetraplegia |
| Increased reflexes LL | Yes | Yes | Yes (ankles abolished) | Yes (ankles abolished) | Yes (ankles abolished) | Not awakened |
| Increased reflexes UL | Yes | Yes | Yes | Yes | Yes | Not awakened |
| Extensor plantar response | Yes | Yes | Yes | Yes | Yes | Indifferent |
| Hoffman sign | NA | NA | NA | NA | NA | NA |
| Decreased vibration sense at ankles | Mild | Mild | NA | NA | No | NA |
| Urinary symptoms | Urinary retention, pollakiuria | No | Incontinence | Incontinence | Incontinence | Incontinence |
| Cerebellar gait | NA | No | No | No | No | NA |
| Cerebellar signs UL | Postural tremor | Postural tremor | No | No | No | NA |
| Dysarthria | No | No | Pseudobulbar, loss of speech (age 30) | Pseudobulbar | Spastic | No speech ever |
| Cognitive impairment | Intellectual deficit IQ 49 | Intellectual deficit IQ 35‐50 | ID, progressive deterioration | ID, progressive deterioration | ID, progressive deterioration | Profound |
| Cutaneous findings | No | No | No | No | No | No |
| Ocular findings | NA | NA | NA | NA | Probable cataract (on neurological examination) | NA |
| Other clinical features | Microcephaly (HC 52 cm, −2 SD), facial dysmorphy | Microcephaly (HC 52 cm, −2 SD), facial dysmorphy | Microcephaly, growth retardation, facial dysmorphy; generalized muscle atrophy | Microcephaly, short stature, generalized muscle atrophy | Mild facial dysmorphy, distal amyotrophy (UL, LL) | Severe growth retardation, cyphoscoliosis, archaic reflexes, extreme muscle atrophy |
| MRI | Normal brain MRI | NA | NA | NA | CC atrophy, periventricular white matter anomalies, mild cortical atrophy | NA |
CC = corpus callosum; CCFS = composite cerebellar functional severity score; ENMG = electro-neuro-myogram; HC = head circumference; ID = intellectual delay; L = left; LL = lower limbs; MD = motor delay; MRC = medical research council; NA = not available; PMD = psychomotor delay; R = right; UL = upper limbs.
Clinical characteristics of patients with ALDH18A1 mutations: autosomal recessive families
| Family N°/Origin . | FSP856/Spain . | SR45/Portugal . | ||||
|---|---|---|---|---|---|---|
| ALDH18A1 variant/Inheritance | p.Asp715His, p.Asp715His/Recessive | p.Arg128His, p.Leu637Pro/Recessive | ||||
| Individual N° (sex) | 18 (M) | 19 (M) | II:3 (F) | II:4 (F) | II:6 (M) | II:9 (F) |
| Age at exam (years) | 42 | 39 | 44 | 49 | 46 | 43 |
| Age at onset (Years) | 7 | 7 | <1 | <1 | <1 | <1 |
| Symptoms at onset | Toe walking, ID, speech delay | ID, gait difficulties | MD, growth retardation | MD, growth retardation | PMD | Severe MD, growth retardation |
| Disease duration (years) | 35 | 32 | 44 | 49 | 46 | 43 |
| Disability score (max 7) | 6/7 | 3/7 | 7/7 | 7/7 | 6/7 | 7/7 |
| Spasticity at gait | Severe | Moderate | Severe, ambulation lost at 30 | Severe | Severe, ambulation lost at 15 | Severe, no ambulation |
| Spasticity at rest | Severe | Moderate | Severe Ashworth 4/4 | Severe Ashworth 3/4 UL; 4/4 LL | Severe Ashworth 4/4 LL; 2/4 UL | Severe Ashworth 4/4 |
| Weakness | Proximal, distal | No | Tetraplegia, drop-feet | Tetraparesia, drop-feet | MRC grading LL 0/5, UL 4/5 | Tetraplegia |
| Increased reflexes LL | Yes | Yes | Yes (ankles abolished) | Yes (ankles abolished) | Yes (ankles abolished) | Not awakened |
| Increased reflexes UL | Yes | Yes | Yes | Yes | Yes | Not awakened |
| Extensor plantar response | Yes | Yes | Yes | Yes | Yes | Indifferent |
| Hoffman sign | NA | NA | NA | NA | NA | NA |
| Decreased vibration sense at ankles | Mild | Mild | NA | NA | No | NA |
| Urinary symptoms | Urinary retention, pollakiuria | No | Incontinence | Incontinence | Incontinence | Incontinence |
| Cerebellar gait | NA | No | No | No | No | NA |
| Cerebellar signs UL | Postural tremor | Postural tremor | No | No | No | NA |
| Dysarthria | No | No | Pseudobulbar, loss of speech (age 30) | Pseudobulbar | Spastic | No speech ever |
| Cognitive impairment | Intellectual deficit IQ 49 | Intellectual deficit IQ 35‐50 | ID, progressive deterioration | ID, progressive deterioration | ID, progressive deterioration | Profound |
| Cutaneous findings | No | No | No | No | No | No |
| Ocular findings | NA | NA | NA | NA | Probable cataract (on neurological examination) | NA |
| Other clinical features | Microcephaly (HC 52 cm, −2 SD), facial dysmorphy | Microcephaly (HC 52 cm, −2 SD), facial dysmorphy | Microcephaly, growth retardation, facial dysmorphy; generalized muscle atrophy | Microcephaly, short stature, generalized muscle atrophy | Mild facial dysmorphy, distal amyotrophy (UL, LL) | Severe growth retardation, cyphoscoliosis, archaic reflexes, extreme muscle atrophy |
| MRI | Normal brain MRI | NA | NA | NA | CC atrophy, periventricular white matter anomalies, mild cortical atrophy | NA |
| Family N°/Origin . | FSP856/Spain . | SR45/Portugal . | ||||
|---|---|---|---|---|---|---|
| ALDH18A1 variant/Inheritance | p.Asp715His, p.Asp715His/Recessive | p.Arg128His, p.Leu637Pro/Recessive | ||||
| Individual N° (sex) | 18 (M) | 19 (M) | II:3 (F) | II:4 (F) | II:6 (M) | II:9 (F) |
| Age at exam (years) | 42 | 39 | 44 | 49 | 46 | 43 |
| Age at onset (Years) | 7 | 7 | <1 | <1 | <1 | <1 |
| Symptoms at onset | Toe walking, ID, speech delay | ID, gait difficulties | MD, growth retardation | MD, growth retardation | PMD | Severe MD, growth retardation |
| Disease duration (years) | 35 | 32 | 44 | 49 | 46 | 43 |
| Disability score (max 7) | 6/7 | 3/7 | 7/7 | 7/7 | 6/7 | 7/7 |
| Spasticity at gait | Severe | Moderate | Severe, ambulation lost at 30 | Severe | Severe, ambulation lost at 15 | Severe, no ambulation |
| Spasticity at rest | Severe | Moderate | Severe Ashworth 4/4 | Severe Ashworth 3/4 UL; 4/4 LL | Severe Ashworth 4/4 LL; 2/4 UL | Severe Ashworth 4/4 |
| Weakness | Proximal, distal | No | Tetraplegia, drop-feet | Tetraparesia, drop-feet | MRC grading LL 0/5, UL 4/5 | Tetraplegia |
| Increased reflexes LL | Yes | Yes | Yes (ankles abolished) | Yes (ankles abolished) | Yes (ankles abolished) | Not awakened |
| Increased reflexes UL | Yes | Yes | Yes | Yes | Yes | Not awakened |
| Extensor plantar response | Yes | Yes | Yes | Yes | Yes | Indifferent |
| Hoffman sign | NA | NA | NA | NA | NA | NA |
| Decreased vibration sense at ankles | Mild | Mild | NA | NA | No | NA |
| Urinary symptoms | Urinary retention, pollakiuria | No | Incontinence | Incontinence | Incontinence | Incontinence |
| Cerebellar gait | NA | No | No | No | No | NA |
| Cerebellar signs UL | Postural tremor | Postural tremor | No | No | No | NA |
| Dysarthria | No | No | Pseudobulbar, loss of speech (age 30) | Pseudobulbar | Spastic | No speech ever |
| Cognitive impairment | Intellectual deficit IQ 49 | Intellectual deficit IQ 35‐50 | ID, progressive deterioration | ID, progressive deterioration | ID, progressive deterioration | Profound |
| Cutaneous findings | No | No | No | No | No | No |
| Ocular findings | NA | NA | NA | NA | Probable cataract (on neurological examination) | NA |
| Other clinical features | Microcephaly (HC 52 cm, −2 SD), facial dysmorphy | Microcephaly (HC 52 cm, −2 SD), facial dysmorphy | Microcephaly, growth retardation, facial dysmorphy; generalized muscle atrophy | Microcephaly, short stature, generalized muscle atrophy | Mild facial dysmorphy, distal amyotrophy (UL, LL) | Severe growth retardation, cyphoscoliosis, archaic reflexes, extreme muscle atrophy |
| MRI | Normal brain MRI | NA | NA | NA | CC atrophy, periventricular white matter anomalies, mild cortical atrophy | NA |
CC = corpus callosum; CCFS = composite cerebellar functional severity score; ENMG = electro-neuro-myogram; HC = head circumference; ID = intellectual delay; L = left; LL = lower limbs; MD = motor delay; MRC = medical research council; NA = not available; PMD = psychomotor delay; R = right; UL = upper limbs.
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