L. Eales

Coexistent variegate porphyria and porphyria cutanea tarda.

VARIEGATE porphyria is inherited as an autosomal dominant disorder with the clinical characteristics of cutaneous involvement and acute attacks, although these features do not always accompany one ...

The effect of bleeding and iron administration on the development of hexachlorobenzene-induced rat porphyria

Abstract 1. 1. Iron overload and iron depletion respectively potentiated and diminished the porphyrinogenic effect of hexachlorobenzene in rats, as assessed by hepatic, renal and colonie activity of uroporphyrinogen decarboxylase and by urinary and faecal porphyrin excretion. 2. 2. In the early phase of hexachlorobenzene intoxication the rat undergoes a definite porphyric phase different from the porphyria cutanea tarda-like phase which occurs later. 3. 3. Preliminary indications are that faecal and urinary uroporphyrin excretion can be correlated with colonie and renal uroporphyrinogen decarboxylase activity respectively.

THE CLINICAL BIOCHEMISTRY OF THE HUMAN HEPATOCUTANEOUS PORPHYRIAS IN THE LIGHT OF RECENT STUDIES OF NEWLY IDENTIFIED INTERMEDIATES AND PORPHYRIN DERIVATIVES

The Republic of South Africa has the dubious distinction of having the highest incidence in the world of two of the ten porphyric entities listed in TABLE 1 . These are variegate porphyria (VP) or South African genetic porphyria, a dominantly inherited, potentially life-threatening disease, and symptomatic porphyria associated with prolonged alcohol abuse (SP-A), often referred t o simply as porphyria cutanea tarda, which results in considerable disability, especially in manual workers. In view of the inordinately high incidence of these two diseases, which affect many thousands of patients in South Africa, it is not surprising that they should feature so prominently in TABLE 2 , which is an analysis of 5 16 porphyric patients who have been studied at Groote Schuur Hospital during the period from 1950 t o the present date. SP-A and VP together account for 90% of our total porphyric experience and this accounts for our research activities being mainly but not exclusively concerned with these two diseases, whose main features are summarized in TABLE 3. Before proceeding further a brief introductory commentary on these two diseases will be given for the benefit of nonmedically oriented scientists.

Liver involvement in erythropoietic protoporphyria (EP)

Abstract 1. 1. Clinical and biochemical evidence of liver involvement was found in 7 patients with EP, in 6 of whom morphological evidence of liver involvement was found on histological examination of the liver biopsy samples. Electron and polarization microscopy were performed on 2 patients. A progression of hepatic dhanges of minimal degree through significant changes in liver function occurred with well marked changes in liver morphology to florid cirrhosis, terminating in massive hepatic necrosis. Our fatal patient was included in an analysis of 12 reported fatal cases of hetatopathy. 2. 2. It is suggested that EP would be better designated as erythrohepatic protoporphyria (EHP).

Drug induced acute porphyric episodes in rats

Abstract 1. 1. Chronic treatment with 0.07% hexachlorobenzene produced a prolonged intermediate porphyric stage in rats very different from the symptomatic porphyria-like syndrome produced by higher doses and longer treatment. 2. 2. Administration of further porphyrinogenic agents to rats in the intermediate porphyric stage induced acute episodes biochemically very similar to the human acute porphyric attack. 3. 3. Few of the excess porphyrins excreted by the rats were of hepatic origin. Faecal porphyrins apparently were synthesized in the intestinal tract, whilst urinary porphyrins originated mainly in the kidney, even during the acute episode.

The effect of carbohydrate on δ-aminolaevulinate synthetase: The role of ribonucleic acid

Abstract 1. Studies are presented which indicate that the induction of δ-aminolaevulinate synthetase by allylisopropylacetamide or ethionine may be inhibited by the administration of metabolisable sugars. This effect is demonstrable both in vivo and in vitro . 2. The δ-aminolaevulinate synthetase-inducing effect of hepatic RNA from an animal fed allylisopropylacetamide or ethionine is considerably less if the animal is fed glucose at the same time. 3. It is suggested that the inhibitory effects of carbohydrates on the induction of the enzyme δ-aminolaevulinate synthetase is mediated through an RNA mechanism and may be due to an interference with the coding of messenger RNA for δ-aminolaevulinate synthetase.

Studies on erythrocyte porphobilinogen deaminase and uroporphyrinogen cosynthetase in Porphyria cutanea tarda

Abstract 1. 1. Erythrocyte porphobilinogen deaminase and uroporphyrinogen cosynthetase were determined using thin-layer chromatography and high-performance liquid chromatography respectively to quantitate reaction products. 2. 2. No difference was observed in the activity of erythrocyte porphobilinogen deaminase between normals and patients with porphyria cutanea tarda, but levels were significantly increased in liver disease, and significantly decreased in chronic renal failure. 3. 3. No evidence of different patterns of uroporphyrin isomer generation was found between haemolysates from controls and from patients with sporadic porphyria cutanea tarda, implying the absence of a possibly inherited defect in uroporphyrinogen cosynthetase.

ROLE OF RIBONUCLEIC ACID IN EXPERIMENTAL PORPHYRIA

Abstract Porphyrin biosynthesis in chick-embryo liver cells can be stimulated by incubation with a ribonucleic acid (R.N.A.) isolated from porphyric rat liver. The R.N.A. fraction contains ribosomal and rapidly labelled components, and the results indicate that it can induce δ-aminolaevulinic-acid-synthetase activity in the chick-liver cells.

The Clinical Chemistry of Variegate Porphyria With Special Reference to the Identification of a New Plasma-Marker Porphyrin

South Africa has the unenviable distinction of having the highest incidence in the world of variegate porphyria (VP) (South African genetic porphyria) (8), with an estimated incidence of approximately 9000 affected persons. How this remarkable situation has come about has been fully documented by Dean (5) in his monograph, which makes it clear that virtually all South African variegate prophyrics are descendants of a daughter of a marriage that took place at the Cape in 16 88 and all are, therefore, members of one huge family. We have investigated one of the four main lines of descent that, as is shown in Figure 1, extends over ten generations and conforms to the pattern of an autosomal dominantly inherited disorder of high expressivity and penetrance. The designation ’variegate,1 which was first applied by Barnes and Dean (1) aptly described the various forms that the disease assumes. They are summarized with their percentage incidence in Table 1.

Unusual porphyrins in porphyric bullous fluid.

Abstract 1. 1. The porphyrins in bullous fluids from two female patients, one with variegate porphyria (VP) and the other with congenital erythropoietic porphyria (CEP), have been analyzed and in each case found to contain an unusual porphyrin, a 4-COOH porphyrin resembling isocoproporphyrin in the VP patient. In the patient with CEP the blister fluid was shown to contain a porphyrin with a Chromatographie mobility compatible with that of isocoproporphyrin.