SHORT REPORT Gender dimorphism in siblings with schizophrenia-like psychosis due to Niemann-Pick disease type C M. Walterfang & M. Fietz & L. Abel & E. Bowman & R. Mocellin & D. Velakoulis Received: 15 February 2009 / Submitted in revised form: 11 May 2009 / Accepted: 19 May 2009 / Published online: 19 July 2009 # SSIEM and Springer 2009 Summary We describe the differential presentation of schizophrenia-like psychosis in two siblings with the Fvariant_ biochemical presentation of adult Niemann- Pick disease type C. The male sibling presented with psychosis at age 16 years and cognitive and motor disturbance at age 25 years, whereas his elder sister, sharing the same mutation but showing less severe biochemical, neuroimaging and ocular motor parame- ters, presented with a similar schizophrenia-like illness with associated cognitive and motor disturbance at age 31 years. Their illness onset, course and response to treatment mirrors the sex dimorphism seen in schizo- phrenia, and is suggestive of an interaction between the neurobiology of their metabolic disorder and sex differences in neurodevelopment. Abbreviation NPC Niemann-Pick disease type C Introduction A range of organic disorders are known to produce schizophrenia-like psychoses in adults, including neu- rological disorders such as epilepsy, CNS neoplasms, infections and trauma, and basal ganglia disorders (Cummings 1996). A number of metabolic disorders are associated with psychosis, most particularly meta- chromatic leukodystrophy, Pelizaeus-Merzbacher dis- ease, and Niemann-Pick disease type C (Walterfang and Velakoulis 2009). We describe two siblings who were diagnosed with schizophrenia in the context of Niemann-Pick disease type C (NPC), whose geno- type was identical but who showed dimorphism in biochemical and clinical parameters, and illness course. Case 1 A 24-year-old caucasian male was referred with an 8-year history of psychotic symptoms, and 2 years of dysarthria and an unsteady gait. He was noted to be a clumsy and perfectionistic child, but otherwise normal developmental milestones were described. At age 16 years he developed auditory and visual hallucina- tions and persecutory delusions, and was treated with typical antipsychotics and electroconvulsive therapy. After a number of relapses and significant residual JIMD Short Report #180 (2009) Online DOI 10.1007/s10545-009-1173-1 Communicating editor: Douglas Brooks Competing interests: None declared M. Walterfang (*) : R. Mocellin : D. Velakoulis Neuropsychiatry Unit, Royal Melbourne Hospital, Level 2, John Cade Building, Royal Melbourne Hospital 3050, Melbourne, Victoria, Australia e-mail: walterfang@mh.org.au M. Fietz Department of Chemical Pathology, Women_s and Children_s Hospital, Adelaide, South Australia, Australia L. Abel : E. Bowman Department of Optometry and Vision Sciences, University of Melbourne, Melbourne, Victoria, Australia