Table 1 Clinical presentation and features of four patients with homozygous mutation c.151_153delAAG of GRXL5
Clinical data | Patient 1 | Patient 2 | Patient 3 | Patient 4 |
|---|---|---|---|---|
Age of onset | 2.5 years | 6 years | 3 years | 6 years |
Age glycine noted | 2.5 years | 8 years | 32 years | 21 years |
Presenting features | Lower limb weakness leading to spastic diplegia | Unsteady gait with frequent falls leading to spastic diplegia | Gait difficulty after febrile seizure at 3 years. Walking frame used by 11 years. Wheelchair bound by 30 years | Frequent falls aged 6 years. Decreased ambulation to 40 m by 13 years. Seizure from age 15 years |
Baseline plasma glycine (µmol/L) | 844–1249 (119–368) | 804 (119–368) | 586–705 (119–368) | 730–1224 (119–368) |
CSF glycine (µmol/L) | 20–26 (3–9) | 15 (3–9) | 28 (3–9) | 53 (3–9) |
CSF/Plasma ratio | 0.02–0.03 (< 0.05) | 0.02 (< 0.05) | 0.04 (< 0.05) | 0.04 (< 0.05) |
Axonal sensory neuropathy | Identified age 14 years | Identified aged 10 years | Identified after age 30 years when assessed | Identified when assessed after 21 years of age |
Age at last review | 20 years | 19 years | 56 years | 45 years |
Clinical features | Spastic quadriparesis with lower limb diplegia. Mainly ambulatory with wheelchair | Episodes of disabling neuropathic pain after exercise. Spastic diplegia | Mainly ambulant with wheelchair. Obsessive compulsive disorder | Wheelchair dependent. Visual impairment. Mild intellectual impairment |
Rankin score | 3 | 3 | 3 | 3 |
Reflex sympathetic dystrophy | Mild bluish discolouration of the feet | Mild bluish discolouration of the feet | Extensive in lower limbs Oedema, hyperesthesia, skin colour changes. Toe amputations | Extensive in lower limbs Oedema, hyperesthesia, skin colour changes. No venous insufficiency |
Peripheral nerve/electrophysiology | Impaired vibration and joint position sense in the lower limb. Absent CMAP in CP and posterior tibial | impaired vibration and joint position sense in the lower limb. Absent | Reduced sensation, impaired vibration and joint position sense in the lower limb absent Ankle jerks | Reduced sensation, impaired vibration and joint position sense in the lower limb. Absent Ankle jerks. Absent sensory/motor AP lower limbs-present upper limbs |
Fundoscopy | Normal | Mild pallor of the discs | Bilateral Optic disc pallor | Severe disc pallor-atrophy |
Cognition | Age appropriate basic language. Difficulties with complex high level language processing tasks, executive and attention problems | Academically gifted attending undergraduate university Bachelor of Science | Normal neuropsychometric test age 47 years | Did not finish school. Aged 39 years—neuropsychometric test—borderline low intellectual function |
MRI brain | Persistent white matter signal changes | Mild focal white matter signal changes at 9 years improved by 15 years | Normal at age 49 years | Normal at age 38 years |