Acute intermittent porphyria: New morphologic and biochemical findings

Abstract

This paper presents the results of postmortem morphologic and biochemical studies on a patient with acute intermittent porphyria (AIP); there was evidence suggesting the syndrome of inappropriate antidiuretic hormone (ADH) release. Examination of the brain revealed injury to the median eminence and bilateral loss of neurones of the supraoptic and paraventricular nuclei. This represents the first correlation of a specific hypothalamic lesion with the syndrome of inappropriate ADH release. The activity of hepatic δ-aminolevulinic acid synthetase (ALA synthetase), a mitochondrial enzyme which normally is rate-limiting for porphyrin biosynthesis, was increased sevenfold above normal. The high level of this enzyme explains the increased porphyrin precursor excretions seen in AIP. Three general mechanisms, including an operator constitutive mutation, have been discussed as possible explanations of the induction of hepatic ALA synthetase.