Joel M. Lamon

Hematin therapy for acute porphyria.

1. A therapeutic trial of intravenous hematin is presented. Eleven cases of AIP and one of VP who did not improve with conventional treatment (high carbohydrate intake) received this new agent. 2. Urinary ALA, PBG and, when possible, uroporphyrin and coproporphyrin were used to monitor the chemical response to the treatment. Objective clinical parameters of hypertension and tachycardia were followed when present in addition to subjective estimates of acute porphyric symptomatology (abdominal pain, backache, extremity pain and paresthesias, weakness, depression, etc.). 3. At a dosage of approximately 3 mg/kg, diminution of urinary ALA and PBG excretion was achieved in every patients. Hypertension and tachycardia improved in those instances where they were observed in association with the attack. Also, subjective improvements in the clinical status of the patients were observed frequently. 4. Hematin appears to be a promising therapeutic agent for the treatment of acute attack forms of porphyria.

Neurotoxic aspects of porphyrinopathies: Lead and succinylacetone

Abstract Neurotoxic effects of heavy metals and polyhalogenated hydrocarbons frequently occur at low levels of exposure, in some cases below those levels where direct toxic actions of these compounds have been demonstrated. Since alterations in heme synthesis are effects common to many of these compounds, the potential role of altered heme synthesis in producing or contributing to their neurotoxicity was studied. Rats with acute and chronic lead exposure were compared to rats whose heme synthesis was inhibited by succinylacetone, as a semichronic model of the hereditary heme synthesis disorder, acute intermittent porphyria. Both treatments produce significant inhibition in activity of the enzyme δ-aminolevulinic acid dehydrase and elevations in the heme precursor δ-aminolevulinic acid (ALA) in tissues and urine. Associated with increased ALA is a significant inhibition of neurotransmission utilizing the amino acid γ-aminobutyric acid (GABA), expressed chemically and behaviorally. The results suggest that in addition to their direct molecular neurotoxicity, porphyrinopathic compounds such as lead may, through altering heme synthesis, adversely affect the brain at low levels of exposure.