Table 1.
Psychotic symptoms and response to treatment in previous cases
| Study | Variant | Psychotic symptoms | Dopaminergic therapy* | Antipsychotic medications (total daily dose) | Treatment response | Antipsychotic impact on motor functioning |
|---|---|---|---|---|---|---|
| Di Fonzo et al. [16]; Chien et al. [17] | Homozygous missense variant in ATP13A2 NM_022089.1, c.[1510 g > c]; c.[1510 g > c], p.[(Gly504Arg)]; [(Gly504Arg)] | VH | yes |
1. haloperidol (NR) 2. quetiapine (50 mg) |
1. NR 2. temporary improvement |
1. NR 2. unclear |
| Behrens et al. [18] | Compound heterozygous variants in ATP13A2, no transcript reported: c.[3057delC]; [c.1306 + 5G > A] | AH, VH, paranoia, confusion | NR | thioridazine (25 mg) | improvement | worsening |
| Abbas et al. [19] | Homozygous missense variant in ATP13A2, reported on Ensembl transcript ENST00000341676: c.[2525T > C]; [2525T > C], p.[(Leu842Pro)]; [(Leu842Pro)] | AH, VH, “excessive fear” | yes |
1. risperidone (NR) 2. olanzapine (NR) 3. quetiapine (NR) 4. levosulpiride (NR) 5. clozapine (25 mg) |
1. NR 2. NR 3. NR 4. NR 5. improvement |
1. NR 2. NR 3. NR 4. NR 5. NR |
| Pietrzak et al. [20] |
Compound heterozygous variants in ATP13A2, no transcript reported: c.[2366_2367delTC]; [2209 C > T], p.[(Leu789Argfs*15)]; [(Gln737*)] |
AH, paranoia | yes |
1. olanzapine (2.5 mg) 2. quetiapine (50 mg) |
1. temporary improvement 2. temporary improvement (in combination with olanzapine) |
1. NR 2. NR |
| Balint et al. [21] | Compound heterozygous variants in ATP13A2 NM_022089.4: c.[1472_1473del]; [c.2567_2568del], p.[(Gln491Argfs*29)]; [(Pro856Argfs*26)] | VH, paranoia | yes |
1. “neuroleptics” (NR) 2. aripiprazole (2.5 mg) |
1. NR 2. improvement, possibly remission |
1. worsening 2. worsening |
| McNiel-Gauthier et al. [22] | Homozygous variant in ATP13A2, no transcript reported: c.[2126G > C]; [2126G > C], p.[(Arg709Thr)]; [(Arg709Thr)] | auditory and visual illusions, paranoia, ideas of reference | yes | aripiprazole (2–3 mg) | improvement | no definitive worsening |
AH = auditory hallucinations; NR = not reported; VH = visual hallucinations
*variability existed across cases regarding when dopaminergic therapy was started relative to psychosis onset