Clinical course
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Normal birth and early development
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Slow onset of developmental delay
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Hypotonia, often with vomiting and failure to thrive
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Seizures, often intractable, before a progressive deterioration
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Clinically apparent hepatic dysfunction, usually terminal
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Death, usually before the age of three years
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Investigations may show the following
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Liver function tests may be abnormal before the onset of seizures
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EEG shows slow activity with high amplitude, mixed with low amplitude high frequency polyspikes
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VEP are absent, asymmetrical, or with an ill defined initial component, with a normal electroretinogram2
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There is progressive cerebral atrophy on cranial imaging, most marked in the occipital region
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Liver pathology shows severe microvesicular fatty change, diffuse bile duct proliferation, bridging fibrosis, a disorganised hepatic architecture, with ongoing hepatocyte necrosis
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Macroscopic brain pathology shows a variably distributed thinned, granular, and discoloured cortical ribbon, typically involving the calcarine cortex
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Brain pathology typically affects the striate and occipital cortex and ranges from a mild superficial astrocytosis, through an increasingly deep sponginess, nerve cell loss and gliosis, to a thin and disorganised cortical ribbon, with hypertrophic astrocytes replacing nerve cells and a prominent vascular component
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Atypical forms exist, with a fulminant course with seizures predominating, a prolonged survival, or late presentations,9 sometimes with an axonal neuropathy15
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