Neuropathy in latent hereditary hepatic porphyria.

Peripheral nerve conduction velocoties were measured in 20 patients with acute intermittent porphyria and five with variegate porphyria and in 25 controls matched for age and sex. None of the porphyric patients had acute symptoms on examination, and nine had never had symptoms. Compared with the controls, patients had a significantly slower conduction velocity of the slower motor fibres of the ulnar nerve (P less than 0-001) and a slower sensory conduction velocity of the ulnar and median nerves (P less than 0-05). There was no significant difference between the patients and controls in the maximum motor conductionvelocity of the median, ulnar, deep peroneal, or posterior tibial nerves. Slight peripheral neuropathy seems to be associated with latent hereditary hepatic porphyria, even in patients who have never had symptoms.     

Porphyrins and porphyrinogen carboxy-lase in hexachlorobenzene-induced porphyria.

1. Qualitative and quantitative studies of the porphyrins and the porphyrinogen carboxylyase of the liver, spleen, kidney, harderian gland and erythrocytes from normal rats and from those hexachlorobenzene-induced porphyria were carried out. 2. Hexachlorobenzene has no effect on erythrocyte porphyrin content, but produces a decrease in that of Harderian gland and an increase in the porphyrin content of the kidney and spleen, and a marked increase in the liver (1 mumol/g of tissue). Octacarboxylic (isomer III) and heptacarboxylic porphyrins accumulated in kidney, spleen and liver, the former porphyrin being predominant. 3. Hexachlorobenzene has no effect on the activity of porphyrinogen carboxy-lase in erythrocytes; there is a slight decrease in enzyme activity in the Harderian gland, and a marked decrease in the liver and kidney enzyme activities. In the liver the removal of each carboxyl group from uroporphyrinogen III appears to be affected by this treatment. 4. The liver is the principal site of action of hexachlorobenzene, with the kidney next in decreasing order of effect, and erythropoietic tissue is unaffected. The marked decrease in porphyrinogen carboxy-lyase activities observed in liver and kidney could explain the high accumulation of octacarboxylic and heptacarboxylic porphyrins found in these tissues. 5. The results are discussed in relation to changes promoted by hexachlorobenzene in other enzymes of the haem pathway.     

Biochemistry of porphyria

• 1.1. The porphyrias are a group of metabolic disorders arising from defects in the haem biosynthetic pathway. Most forms are inherited as Mendelian autosomal dominants, but some types are recessive and others acquired through exposure to porphyrinogenic drugs and chemicals. There is a linked group of diseases, which are not porphyrias, but have in common alterations of haem biosynthesis.
• 2.2. The processes of haem biosynthesis are now well understood and the molecular biology of the functions and dysfunctions in the porphyrias are currently an area of intensive investigation.
• 3.3. The acute porphyrias. Acute Intermittent Porphyria, Variegate Porphyria and Hereditary Coproporphyria are of most importance since attacks of these may be life-threatening.
• 4.4. These diseases that usually present with a neurovisceral attack are characterized by excess production of the porphyrin precursors, 5-aminolaevulinate and porphobilinogen because of lowered activity of Porphobilinogen deaminase.
• 5.5. A variety of factors may precipitate these attacks including various drugs, alcohol, smoking, dieting or fasting and variations in steroid hormone levels.
• 6.6. The non-acute porphyrias are largely dermatological conditions, which present clinically as cutaneous photosensitivity. The dermatological changes are caused by the photosensitizing properties of circulating porphyrins and are accompanied by systemic effects of these porphyrins.

     

The role of iron in experimental porphyria and porphyria cutanea tarda

Porphyria cutanea tarda (PCT) and experimental porphyria are characterized by a decreased activity of the enzyme uroporphyrinogen decarboxylase, and accumulation of uroporphyrins and heptacarboxylporphyrins in the liver. Iron (Fe) plays an important role in PCT and experimental porphyria. Biochemically and electron microscopically, we examined the relationship between Fe and porphyrins in liver tissue of C57BL/10 mice made porphyric by administration of iron dextran as Imferon^® (IMF), and in liver biopsies of patients with symptomatic PCT. Accumulation of uroporphyrins and heptacarboxylporphyrins, and an increased amount of Fe were observed in livers of mice treated with IMF and in liver biopsies of patients with PCT. In mice treated with IMF, the activity of uroporphyrinogen decarboxylase was decreased. Both in livers of mice treated with IMF and in livers of patients with PCT, needle-like structures, representing uroporphyrin crystals, were observed by electron microscopy. Uroporphyrin crystals and Fe (as ferritin) were observed in the same hepatocyte. Moreover, there was a striking morphological correlation between uroporphyrin crystals and ferritin-Fe, suggesting a role for (ferritin-)Fe in the pathogenesis of porphyria.