Table 1 Summary of findings in family RP-0482 and comparison with other PRS-I deficiency disorders (adapted from de Brouwer et al. [11])
From: Expanding the phenotype of PRPS1 syndromes in females: neuropathy, hearing loss and retinopathy
IV:3 | IV:2 | III:2 | Arts syndrome | CMTX5 | DFN2 | |
|---|---|---|---|---|---|---|
Date of birth | 1978 | 1976 | 1943 | |||
Symptoms (age at diagnosis) | ||||||
Ophthalmological | ||||||
Retinitis Pigmentosa | + (14y) | + (23y) | + (47y) | - | - | - |
Night blindness | ++ (4y) | + (16y) | + | - | - | - |
Visual field constriction | ++ | + | + | - | - | - |
Visual acuity loss | ++ (4y) | - | ++ | - | - | - |
ERG alteration | ++ | +/− | ++ | - | - | - |
Pigmentary changes at fundus | + | +/− | + | - | - | - |
Macular atrophy | ++ | + | + | - | - | - |
Optic atrophy | + (5y) | + (16y) | + (47y) | + | + (~10y) | + |
Nystagmus | + (Congenital) | - | - | - | - | - |
Cataracts | + | - | + | - | - | - |
Hyperopia | + | + | +/− | - | - | - |
Hearing impairment | ++ (21y) | - | + (50y) | ++ | + | + |
Neurological | ++ (34y) | - | + (55y) | |||
Mild developement delay | +/− | - | - | + | - | - |
Hypotonia | + | - | - | + | + | - |
Delayed motor development | - | - | - | + | - | - |
Peripheral neuropathy | ++ | - | + | + | + | - |
Pes cavus | + | - | - | NR | NR | NR |
Loss of deep tendom reflexes | - | - | - | - | + | - |
Cerebellar Atrophy | ++ | - | + | |||
Ataxia | + | - | + | + | + | - |
Essential tremor | + | + | + | |||
Symptoms in carrier females | +++ | + | ++ | Isolated and milder | Hearing loss | None |
PRS activity erythrocytes (nmol/h/mg Hb) (Reference: 70–126) | Erythrocytes: 10 | Erythrocytes: 41 | Erythrocytes: 65 | Erythrocytes: No activity | Fibroblasts: Decreased | Erythrocytes and fibroblasts: Decreased |
Fibroblasts 13-fold decrease | ||||||
EBV-LCLs: normal | ||||||
Structural effect of mutation | Whole protein structure? | ATP site and allosteric sites I and II | ATP site and allosteric site I | Local structure | ||