EVOLUTION OF HEPATIC CIRRHOSIS IN PEROXISOMAL DYSFUNCTION DISORDERS: THE SPECTRUM OF HISTOPATHOLOGIC ABNORMALITIES

Abstract

Patients with peroxisomal dysfunction disorders lack peroxisomes or certain peroxisomal enzymes. Assay of activity of the peroxisomal membrane enzyme dihydroxyacetone phosphate acyl transferase (DHAP-AT) provides a biochemical test for identifying patients with peroxisomal disorders. We report 8 patients with a spectrum of peroxisomal disorders. All patients have dysmorphia, failure to thrive and hepatomegaly. Serum transaminase levels ore elevated and activity of DHAP-AT is reduced. All patients have other chemical abnormalities associated with peroxisomal dysfunction. One infant had Zellweger's cerebro-hepato-renal syndrome (CHRS) and died at age 10 months. The other patients presented with either a variant of Zellweger's CHRS or neonatal adrenoleukodystrophy (4), dicarboxylic aciduria (1), infantile Refsums' disease (1) or chrondrodysplasia punctata (1). Histopathologic changes in the liver include micronodular cirrhosis (2), fibrosis (4), and paucity of intrahepatic ducts (2). In addition, there was accumulation of hepatocyte hemosiderin in 1 patient and abundant deposition of glycogen in 3 patients. Peroxisomal disorders present with a variety of clinical problems. Infants with failure to thrive, hepatomegaly and suggestive dysmorphia should be screened by assaying DHAP-AT.