Porphyria cutanea tarda (PCT) was diagnosed in 27 women aged 23-48 years (mean, 35 years) who had been under oral-hormonal-contraceptive medication for 1-18 years, in 3 women under substitutional estrogen treatment in the menopause, and in 2 men aged 65 and 76 years after estrogen treatment of prostatic carcinoma. In all patients, total urinary porphyrin excretion was elevated, with an average uro- and heptacarboxyporphyrin predominance of 88%, thus proving PCT. Of the patients, 84% showed a significant decrease of erythrocyte uroporphyrinogen-decarboxylase (UD; EC 4.1.1.37) activity to approximately 50% of control levels suggesting a hereditary predisposition for the development of a chronic hepatic porphyria. Estrogens and alcohol are capable of reducing hepatic UD activity. Women with hereditary red cell UD deficiency may be regarded as predisposed to PCT when under estrogen intake, especially in combination with the potentiating influence of alcohol and chronic liver disease. Normal erythrocyte UD values in patients with additive alcohol consumption may implicate a stronger inhibitory effect for alcohol on UD, suggesting a merely toxic form of chronic hepatic porphyria.

Doss, Sixcl-Dietrich and Verspohl: "Glucose effect" in hepatocyte culture and in acute hepatic porphyrias 505 J. Clin. Chem. Clin. Biochem. Vol. 23, 1985, pp. 505-513 (Received January 26/May 8, 1985) Summary: The effect of glucose on drug-promoted induction of porphyrin synthesis was studied in chick embryo liver cell culture with and without the addition of exogenous -aminolaevulinic acid (ALA). Induction of ALA synthase was abolished by haemin or glucose. Less than 10% 0f porphobilinogen is converted into protoporphyrin. Protoporphyrin synthesis cannot be enhanced by high ALA concentrations. The conversion of exogenous ALA into porphyrins decreases with increasing concentrations of ALA from 0.1 to 2.0 mmol/1, whereas porphobilinogen accumulates, thus reflecting the rate limiting function of Uroporphyrinogen synthase, which is not influenced by glucose. This needle-eye-like function of Uroporphyrinogen synthase within the porphyrin biosynthetic chain explains the urinary increase of ALA and porphobilinogen in the acute phase of variegate and coproporphyria, similar to that in acute intermittent porphyria. i * The "glucose effect" was also investigated in vivo in humans in 32 courses of hereditary acute hepatic . v porphyrias (acute intermittent porphyria, variegate porphyria, coproporphyria and porphobilinogen synthase defect porphyria). Patients were treated with high carbohydrate intake (~500 g/24 h), mainly in the form of glucose infusions. There was a resulting coiisistent and highly significant decrease of porphyrin biosynthesis metabolites, accompanied by clinical improvement in most of the patients. "Glucose-Effeki" und limitierende Funktion der Uroporphyrinogen-Synthase auf den Porphyrinstoffwechsel in der Leberzellkultur in Bezug auf die akuten hepatischen Pörphyrien des MenschenZusammenfassung: Die Wirkung von Glucose auf die Arzneimittel-vermittelte Induktion der Porphyrinsynthese wurde in Hühnerembryo^Leberzellkulturen unter Bedingungen mit endogener und exogener 5-Aminolävulinsäüre (ALS) studiert. Die Induktion der ALS-Synthase konnte durch Hämin oder Glucose aufgehoben werden. Wenjger als 10% Porphobilinogen wird in Porphyrine konvertiert. Die Synthese von Protoporphyrin kann unter hohen ALS-Konzentrationen nicht gesteigert werden. Die Umwandlung exogener ALS in Porphyrine fällt mit steigender Konzentration der ALS von 0,1 bis 2,0 mmol/1, während Porphobilinogen akkumuliert: Hierin spiegelt sich die Umsatz-limitierende Funktion der Uroporphyrinogen-Synthase, die nicht durch Glucose beeinflußt wird". Die Nadelöhr-ähnliche Funktion der Uroporphyrinogen-Synthase innerhalb der Porphyrinbiosynthesekette erklärt den Anstieg von ALS und Porphobilinogen im Urin in der akuten Phase der Porphyria variegata und der Koproporphyrie, welcher demjenigen bei akuter intermittierender Porphyrie ähnlich ist.Der "Glucose-Effekt" in vitro wurde mit dem in vivo beim Menschen verglichen und bei 32 Verläufen hereditärer akuter hepatischer Porphyrieii untersucht (akute intermittierende Porphyrie, Porphyria varie...

Diabetic oral glucose tolerance test together with hyperinsulinemia in a patient with decompensated acute intermittent porphyria is contrasted to normal findings in compensated acute intermittent porphyria (AIP). Results point to the essential role of insulin for the depression of porphyrin precursor overproduction as a mediator of the "glucose effect".

A case of acute lead poisoning due to intravenous injection of lead acetate is reported. The patient developed clinical and biochemical symptoms characteristic for acute hepatic porphyrias. Elevated urinary 5-aminolaevulinic acid and low porphobilinogen correlated to a lead-induced inhibition of 5-aminolaevulinic acid dehydrase with diagnostically indicative reactivation rates by zinc and dithiothreitol. Urinary coproporphyrin excretion was also increased. Additional findings included anaemia and toxic hepatitis. Under the influence of elimination therapy with D-penicillamine pathologic parameters normalized. Except for transient neuralgic pains the patient did not experience any neurologic dysfunctions, thus contrasting the findings in chronic lead intoxication.

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