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 . 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 . 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 g / l ( 15200 ) . 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 . 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 . there was no history of substance abuse . on mental state examination , she was cooperative but only established superficial rapport 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 . g / l  ( 115150 ) with normal platelet and white cell counts and b12 and folate levels . 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 ) . a screen for lysosomal and other storage disorders on peripheral blood lymphocytes and cultured fibroblasts was normal . neuropsychological assessment showed a woman of low - average to average premorbid intellect , but demonstrating borderline general intellectual ability suggesting a significant decline . she performed significantly better on non - verbal than verbal tasks , which were poor , in addition to poor verbal memory . working memory was very poor , and psychomotor speed and speed of information processing was slowed . she displayed good performances on frontal - based tasks tapping into generating new strategies , response monitoring , inhibition , planning and organization , and mental set - shifting , although she was at times significantly slower than her age - peers . these deficits were also borne out in an occupational therapy assessment , where her deficits of new learning were manifest in requiring frequent repetition to learn new tasks , and slow mental information processing impaired her ability to deal with everyday financial and logistical tasks . the patient s risperidone was increased to 5 mg per day , with some improvement in her degree of negative symptoms without re - emergence of positive symptoms . ceruloplasmin ( cp ) is a 132-kda glycoprotein that is predominantly synthesized in the liver but does not cross the blood brain barrier and is produced by astrocytes in the cns ( klomp and gitlin 1996 ) . copper atoms incorporated during the synthesis of cp allow it to shuttle electrons and act as a multicopper ferro - oxidase . in iron homeostasis cp oxidises fe ( ferrous iron ) to fe ( ferric iron ) so that the latter can bind to transferrin and be trafficked throughout the body . fe is required as a cofactor for many biological processes but is capable of generating toxic hydroxyl and superoxide free radicals , and hence must be tightly bound to proteins during transport and storage ( de silva et al 1996 ) . cp promotes the loading of iron onto transferrin , allowing fe efflux out of cells and preventing oxidative damage caused by fe ( qian and ke 2001 ; hellman and gitlin 2002 ) . in aceruloplasminemia , an autosomal recessive disorder occurring in 1 in 2 million non - consanguinous births ( miyajima et al 1999 ) , mutations in the cp gene result in absent ferroxidase activity of cp leading to the deposition of iron in the cns , retina , pancreatic cells , liver , spleen , and ovaries ( yoshida et al 1995 ; hellman and gitlin 2002 ) . the astrocyte - specific form of cp plays a key role in regulating iron levels in the cns and in preventing free radical injury ( patel et al 2002 ) . the major sites of cns iron deposition in aceruloplasminemia are the basal ganglia , cerebellar dentate nuclei , red nucleus , thalamus , and hippocampus ( miyajima 2003 ) . the pattern of deposition , which is greatest in the globus pallidus and putamen ( miyajima 2003 ) , occurs in regions where vulnerable perivascular astrocyte populations are distributed ( klomp and gitlin 1996 ) . the sites of greatest iron concentration in healthy individuals are the basal ganglia , red nucleus , and deep nuclei of the cerebellum ( yoshida et al . aceruloplasminemia presents with retinal degeneration , diabetes mellitus and neurological symptoms , usually extrapyramidal signs , dyskinesia , dystonia , and a subcortical dementia in the fifth or sixth decade ( nittis and gitlin 2002 ) . neurological signs may be preceded for many years by diabetes mellitus and anemia due to inefficient iron delivery . mri findings typically show marked t2 hypointensity in these regions of maximal iron deposition ( morita et al . 2005 ) , although may also show subtle posterior white matter tract hyperintensity and subtle superficial cerebral and cerebellar cortical hypointensity ( grisoli et al . 2005 ) . white matter tract changes may reflect a disconnection of projecting fibres from key relay nuclei such as the thalamic nuclei , with subsequent subtle cortical changes ( grisoli et al . 2005 ) . while the clinical presentation was predominantly one of schizophrenia with no classical neurological features of aceruloplasminemia , the imaging findings of thalamic and cerebellar involvement suggest that even at this early stage cns manifestations of aceruloplasminemia are present but neurologically silent . bb s imaging also revealed prominent frontal cortical atrophy , white matter hyperintensities and thinning of the corpus callosum which are not characteristic of cp ( miyajima 2003 ) and no other pathological cause was found for these changes . regional cortical and callosal atrophy of this nature , as opposed to subtle cortical and white matter intensity changes , have not previously been reported in aceruloplasminemia . the mri findings of significant iron deposition in the thalamus and the dentate nucleus of cerebellum may be relevant to her schizophrenia - like presentation . the repeated demonstration of subtle abnormalities in structure and function of the cerebellum in schizophrenia populations has also led to its implication in the development of schizophrenia , possibly due to disruptions to the cerebellothalamo - cortico - cerebellar loop ( andreasen et al . pathology in the thalamus may also disrupt this circuit , and given that the thalamus has similarly been implicated in the pathogenesis of schizophrenia ( clinton and meador - woodruff 2004 ) , it is feasible that iron deposition - related pathology in these regions may be , in a vulnerable brain , psychotogenic . the development of psychosis in bb , atypical for aceruloplasminemia , could be seen to represent an the effects of aceruloplasminemia through pathology in dentate and thalamic regions in bb may have interacted with an early frontal insult , such as perinatal hypoxia or other obstetric complications  known risk factors for the later development of schizophrenia ( cannon et al . 2002a , 2002b )  or with other unknown biological vulnerabilities , to result in schizophrenia - like symptoms during the typical age of onset for the disorder . there is a strong relationship between anatomic abnormalities in the hippocampus , cerebellum and thalamus and schizophrenia ( harrison 1999 ; shenton et al . 2001 ) and iron deposition in these regions during adolescence may have triggered a vulnerability to schizophrenia - like psychosis in this patient .