Alpers disease consists of diffuse cerebral degeneration manifested as 
developmental delay, seizures, vomiting, and progressive neuromuscular 
deterioration, with liver disease and death. We report the clinical course of 
the liver disease, histologic progression of the hepatic lesions, and etiologic 
investigations in five patients (four girls, three kinships). All had grown and 
developed normally until seen at 6 to 36 months of age (mean 20 months), with 
vomiting (n = 5), progressive hypotonia (n = 3), or seizures (n = 2). All had 
been given anticonvulsants, including valproic acid in three. Liver disease was 
noted at a mean age of 35 months (range 9 to 67 months), with hepatomegaly (two 
patients), abnormal hepatic synthetic function (three) or transaminase values 
(three), and cirrhosis in one. Patients survived for a mean of 4.6 weeks (range 
1 to 8 weeks) after the identification of liver disease; all died of hepatic 
failure. Results of evaluation for infectious and metabolic causes of liver 
disease and causes of degenerative neuromuscular disease were negative in all 
patients. Premortem liver biopsy specimens (n = 3) demonstrated an early lesion 
consisting of lobular disarray, microvesicular steatosis, periportal acute and 
chronic inflammation, and individual hepatocyte necrosis. Autopsy findings (n = 
5) consisted of macrovesicular steatosis, massive hepatocyte dropout, and 
proliferation of bile ductular elements, with almost complete replacement of 
hepatocytes by proliferating bile ductular elements in two patients. Brain 
showed characteristic neuronal degeneration. We conclude that Alpers disease can 
be a cause of rapidly progressive liver failure in early childhood. Although the 
cause of this autosomal recessive disease is not known, it does not appear to be 
related to peroxisomal dysfunction.