Schizophrenia-like psychosis and aceruloplasminemia

Schizophrenia-like psychosis and aceruloplasminemia


Schizophrenia-like illnesses occur in a variety of medical and neurological conditions but to date have not been described in association with aceruloplasminemia. Aceruloplasminemia is an autosomal recessive disorder of iron metabolism which leads to iron deposition in the basal ganglia, thalamus, cerebellum and hippocampus and which usually presents in middle age with extrapyramidal symptoms and dementia. We describe a 21-year-old woman on treatment for aceruloplasminemia who presented with schizophrenia-like psychosis and declining function in the absence of neurological signs. Neuropsychological testing showed significant dominant hemisphere deficits. Magnetic resonance imaging showed bilateral iron deposition in the cerebellar dentate nuclei and thalami, frontal atrophy, and periventricular white matter hyperintensities. Functional imaging suggested global hypoperfusion. The clinical, cognitive and imaging findings were not typical for either aceruloplasminemia or schizophrenia alone and the possible relationship between the two disorders is discussed with particular reference to implications for our understanding of schizophrenia.

Keywords: aceruloplasminemia, schizophrenia, psychosis


Numerous medical conditions are known to produce psychotic symptoms that resemble schizophrenia, including metabolic and neurological disorders (Cummings 1996). We describe a young woman with schizophrenia-like psychotic symptoms and functional decline in the context of diagnosed aceruloplasminemia, a disorder which has not been previously associated with psychosis.

Case history

BB was a 21-year-old woman referred for neuropsychiatric assessment on the background of a psychotic illness and a confirmed diagnosis of aceruloplasminemia. BB’s family had noticed an initial 18-month period of functional and social deterioration, poor school performance, social withdrawal, and periods of verbal aggression. She was initially treated by her general practitioner with fluvoxamine, but later deteriorated with frank persecutory delusions, auditory hallucinations, aggression and poor self-care over the subsequent 6 months. The local mental health team began risperidone 3 mg/day, which treated the positive symptoms but did not arrest her functional decline. BB completely avoided all social contact, only watched television and was unable to manage her activities of daily living. She was referred for neuropsychiatric assessment to further elucidate the contribution of the aceruloplasminemia to her cognitive and functional abilities.


BB had no formal psychiatric history. She had mild learning difficulties as a child, but attended mainstream schooling. At age 15 she had seen a school psychologist after telling other students she was going to be reborn as a prince. BB had been diagnosed with aceruloplasminemia at age 20, after detection of abnormal liver function and hyperferritinemia of 1700 μg/L (15–200). Liver biopsy confirmed significant iron overload without fibrosis, and desferrioxamine 20 g thrice weekly was initiated. The diagnosis of aceruloplasminemia was highly suspected because a paternal uncle had been diagnosed with the disorder. The patient and her maternal uncle share a common, unique mutation for this disorder. BB’s uncle had been described by the family as suffering long-standing behavioral problems but had never been given a psychiatric diagnosis. There was a history of consanguinity, with her parents’ grandparents being first cousins.

BB’s delivery was normal but for a prolonged rupture of membranes. She walked at 12 and talked at 15 months. She was a shy and clingy child at school who had verbal and social difficulties. She left school in Year 11 and attended a technical college where she also struggled. She had not worked or attended school since the age of 18. There was no history of substance abuse.

On mental state examination, she was cooperative but only established superficial rapport. Speech was of normal rate and volume with limited spontaneity. Mood was euthymic and affect reactive, although blunted. At the time of assessment there were no psychotic or depressive symptoms and no insight into her previous symptoms or functional impairment.

On bedside cognitive testing, she scored 25/30 on the Mini-Mental State Examination (Folstein et al 1975), and 75/100 on the Neuropsychiatry Unit Cognitive screening tool (NUCOG) (Walterfang et al 2006), each significantly below expected age norms. Hence, the patient was referred for a neuropsychological review, and information from an earlier assessment was obtained as a baseline. Physical examination was unremarkable. She had some mild conjunctival pallor but no Kaiser-Fleischer rings. She had no abdominal organomegaly. There were no abnormal movements, primitive reflexes or other neurological signs.

BB had normal electrolytes, hepatic, renal and thyroid function. Hemoglobin was low at 101 g/L” (115–150) with normal platelet and white cell counts and B12 and folate levels. Serum ferritin was still elevated at 688 μg/L (15–200).

Magnetic resonance imaging (MRI) showed global atrophy, most marked over the frontal lobes. She had a greater-than-expected load of periventricular white matter hyperintensities, and a thin anterior callosum. Iron deposition was evident in the dentate nucleus of the cerebellum and the thalamus, and to a lesser degree throughout the whole cerebral cortex, but not in the basal ganglia (Figure 1). Single-photon emission computed tomography (SPECT) showed global hypoperfusion. MRI of the abdomen showed no evidence of ovarian iron deposition. EEG was normal. A screen for lysosomal and other storage disorders on peripheral blood lymphocytes and cultured fibroblasts was normal.

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