Table 1

Reported clinical findings in Alpers’ syndrome2,4,14

EEG, electroencephalogram; VEP, visual evoked potentials.
Clinical course
  • Normal birth and early development

  • Slow onset of developmental delay

  • Hypotonia, often with vomiting and failure to thrive

  • Seizures, often intractable, before a progressive deterioration

  • Clinically apparent hepatic dysfunction, usually terminal

  • Death, usually before the age of three years

Investigations may show the following
  • Liver function tests may be abnormal before the onset of seizures

  • EEG shows slow activity with high amplitude, mixed with low amplitude high frequency polyspikes

  • VEP are absent, asymmetrical, or with an ill defined initial component, with a normal electroretinogram2

  • There is progressive cerebral atrophy on cranial imaging, most marked in the occipital region

  • Liver pathology shows severe microvesicular fatty change, diffuse bile duct proliferation, bridging fibrosis, a disorganised hepatic architecture, with ongoing hepatocyte necrosis

  • Macroscopic brain pathology shows a variably distributed thinned, granular, and discoloured cortical ribbon, typically involving the calcarine cortex

  • 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

  • Atypical forms exist, with a fulminant course with seizures predominating, a prolonged survival, or late presentations,9 sometimes with an axonal neuropathy15