title: Non-Wilsonian hepatolenticular degeneration: Clinical and MRI observations in four families from south India.
abstract: Non-Wilsonian hepatolenticular degeneration (NWHD) is a heterogeneous neurological disorder occurring secondary to chronic acquired liver disease. Genetically determined familial NWHD is rare, poorly understood, and often mistaken for Wilson's disease (WD). We analysed clinical and MRI profiles of NWHD patients who did not have obvious cause for acquired liver disease, such as alcohol intake or hepatitis. Six patients from four families (four males, two females, mean age: 17.0±standard deviation 7.9years), presenting with chronic extrapyramidal disorder resembling WD and imaging (abdominal ultrasound/MRI) evidence of cirrhosis were studied. They lacked Kayser-Fleischer rings or biochemical and/or genetic evidence of WD. Clinical features included dystonia (n=6), parkinsonism (n=3), tremor (n=1), cerebellar ataxia (n=3), orofacial dyskinesia (n=1), behavioural abnormalities (n=3), and cognitive decline (n=1). Brain MRI revealed T1-weighted hyperintensity in the pallidum (n=6), crus cerebri (n=4), putamen (n=1), caudate (n=1), thalamus (n=1), and red nucleus (n=1) with T2-weighted shortening in some of these regions. Additional findings included giant cisterna magna (n=1), face of giant panda sign (n=1) and thin corpus callosum (n=1). Areas of "blooming" on susceptibility weighted images were noted in two patients in the caudate (n=2) and putamen (n=1). The finding of T1 shortening is distinct from that of WD where the majority of lesions are T1-hypointense and T2-hyperintense. Extrapallidal T1-hyperintensity is also an exceptional observation in NWHD. The MRI appearance of intense T1 shortening coupled with the lack of increased susceptibility changes suggests that the most likely mineral deposited is manganese. The association of this neurological disorder and cirrhosis of the liver in the absence of an acquired liver disease is a distinct disease entity. This syndrome may represent a disorder of manganese metabolism resulting in its toxic deposition.
authors.affiliation: Department of Neurology, National Institute of Mental Health and Neuro Sciences (NIMHANS), Bangalore 560 029, Karnataka, India.
authors.forename: Madhu
authors.initials: M
authors.lastname: Nagappa
authors.affiliation: Department of Neurology, National Institute of Mental Health and Neuro Sciences (NIMHANS), Bangalore 560 029, Karnataka, India. Electronic address: sanjib_sinha2004@yahoo.co.in.
authors.forename: Sanjib
authors.initials: S
authors.lastname: Sinha
authors.affiliation: Department of Neuroimaging and Interventional Radiology (NIIR), National Institute of Mental Health and Neuro Sciences (NIMHANS), Bangalore, India.
authors.forename: Jitender S
authors.initials: JS
authors.lastname: Saini
authors.affiliation: Department of Neurology, National Institute of Mental Health and Neuro Sciences (NIMHANS), Bangalore 560 029, Karnataka, India.
authors.forename: Pradeep
authors.initials: P
authors.lastname: Kallolimath
authors.affiliation: Department of Molecular Reproduction, Development and Genetics, Indian Institute of Science (IISc), Bangalore, India.
authors.forename: Nivedita
authors.initials: N
authors.lastname: Singh
authors.affiliation: Department of Molecular Reproduction, Development and Genetics, Indian Institute of Science (IISc), Bangalore, India.
authors.forename: Arun
authors.initials: A
authors.lastname: Kumar
authors.affiliation: Department of Neurology, National Institute of Mental Health and Neuro Sciences (NIMHANS), Bangalore 560 029, Karnataka, India.
authors.forename: Parayil S
authors.initials: PS
authors.lastname: Bindu
authors.affiliation: Department of Neurology, National Institute of Mental Health and Neuro Sciences (NIMHANS), Bangalore 560 029, Karnataka, India.
authors.forename: Arun B
authors.initials: AB
authors.lastname: Taly
mesh_terms: D000293:Adolescent; D000328:Adult; D001480:Basal Ganglia Diseases / Q000150:complications* / Q000378:metabolism / Q000473:pathology*; D005260:Female; D006801:Humans; D007194:India; D008103:Liver Cirrhosis / Q000150:complications* / Q000378:metabolism / Q000473:pathology*; D008279:Magnetic Resonance Imaging; D008297:Male; D008345:Manganese / Q000378:metabolism*; D008875:Middle Aged; D010375:Pedigree
chemical_list: D008345:Manganese
keywords: Liver dysfunction; MRI; Manganese; Non-Wilsonian hepatolenticular degeneration; Pallidal hyperintensity; Wilson’s disease