Hereditary uroporphyrinogen-decarboxylase deficiency predisposing porphyria cutanea tarda (chronic hepatic porphyria) in females after oral contraceptive medication

Abstract

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.

Porfiria cutânea tardia

“…55 Estrogens may also act inhibiting Urod in the liver of patients with genetically reduced enzyme. 56 Hexachlorobenzene (HCB) -Used as a fungicide, caused an "epidemic" of toxic PCT in southeast Turkey in 1952. It was also used as a pesticide in wheat seeds, but due to famine, thousands of people, mostly children ate bread made with this wheat and presented toxic PCT.…”

Precipitating factors of porphyria cutanea tarda in Brazil with emphasis on hemochromatosis gene (HFE) mutations. Study of 60 patients

“…Individuals suffering from PCT are apparently genetically predisposed to developing UROD deficiency in response to liver damage. 3 Iron acts as a switch that controls the generation of UROD inhibitors, commencing a vicious cycle of UROD inactivation; its removal allows restoration of UROD activity. 4 Remission after phlebotomy and treatment failure when iron supplement is administered, suggests that iron has an important role in the pathogenesis of the disease.…”

Hemochromatosis (HFE) Gene Mutations and Response to Chloroquine in Porphyria Cutanea Tarda

“…5,[8][9][10] Compared with healthy controls, a high frequency of the C282Y mutation (ranging from 11%-47%) in the HFE gene, the major genetic alteration in genetic hemochromatosis, has been found in patients with PCT from the United Kingdom, the Netherlands, southern Italy, Spain, Australia, and the United States. [11][12][13][14][15][16][17][18] In a study from northern Italy, however, C282Y mutations occurred as frequently in patients with PCT as in controls (1.5%), whereas the H63D mutation was significantly increased in patients with PCT.…”