Medical case narrative
A young man whose "treatment-resistant psychosis" resolved when the real disease was treated
What happened
A young man in Hungary (unnamed in the published report) developed a severe, therapy-resistant psychotic episode at age 20½: visual hallucinations, paranoid thoughts and distortion of reality, then persecutory delusions, sleep disturbance, anxiety, and bizarre paranoid ideas, requiring psychiatric inpatient care. Over roughly fifteen weeks he was treated in sequence with olanzapine (10, then 20 mg/day), haloperidol, and aripiprazole, with little or no improvement. The report states no formal schizophrenia diagnosis for him; its framing is therapy-resistant psychosis, and this entry keeps that wording.
What it looked like
The red flags ran back to childhood and had been read as non-specific: attention deficit and delayed reactions from preschool age; involuntary torsion-like arm movements at age 10, misjudged as a bad habit or tic; at 14, slurred speech, coordination problems, frequent falls, and central hearing loss; later dyslexia and dysgraphia; from 17, rapid fine-motor decline and difficulty swallowing. On re-examination: mild facial weakness, diminished throat reflexes, dysarthria, cerebellar ataxia, dystonia of the hands, and vertical supranuclear gaze palsy on looking down — plus an enlarged spleen, and by 20½ moderate diffuse cerebral atrophy on MRI (it had been normal at 17).
What the labs found
The combination of the enlarged spleen — estimated volume 440 mL — the gaze palsy, and the gradual motor decline suggested Niemann-Pick disease type C. Bone-marrow biopsy showed foamy macrophages of the kind seen in this condition; skin-cell filipin staining was inconclusive, with cholesterol esterification at 17% of normal; NPC1 sequencing confirmed the diagnosis: compound heterozygous mutations c.3019C>G (p.Pro1007Ala), inherited from his mother, and c.3182T>C (p.Ile1061Thr), inherited from his father.
What changed
Miglustat, the disease-specific drug, was started at 3 × 200 mg/day about six weeks after the psychosis began. His antipsychotics had to be stopped anyway after a dystonic crisis. His psychotic symptoms had gradually resolved about three months after miglustat was started — and about two weeks after the antipsychotics were stopped, two changes at once, and this entry credits them that way rather than the drug alone. The psychosis did not recur in three years of follow-up, and MRI at 22 and 23 showed no progression of the cerebral atrophy. At 24 he remained ambulatory, capable of self-care and doing sports daily, with his parents supervising him around the clock; at 23 his overall IQ was 79 (verbal 92, performance 68) — average verbal intelligence alongside severely impaired visuo-motor, mathematical, and reasoning skills. A later review of his case says recovery came "after 1 year of miglustat therapy"; the original report's roughly three-month timeline is the one this entry follows, and the discrepancy is noted here rather than smoothed over.
The test that told the story
NPC1 gene sequencing — set in motion by the spleen, the downward-gaze palsy, and a decade of "non-specific" signs read together at last.
Sources: Szakszon et al., European Journal of Paediatric Neurology 2014;18:75–78 (full case report, all values); Patterson et al., Orphanet Journal of Rare Diseases 2018 (review re-report of this case).