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Liver Diseases
Published in George Feuer, Felix A. de la Iglesia, Molecular Biochemistry of Human Disease, 2020
George Feuer, Felix A. de la Iglesia
Erythropoietic porphyrias are very rare; the defect is in the red blood cell related to a genetically determined abnormality in porphyrin synthesis. Congenital erythropoietic porphyria is a recessive disease characterized by severe photosensitivity, which starts at birth or soon after, and persists throughout life. It leads sometimes to very severe scarring and deformities. Large quantities of porphyrins are deposited in the bones, teeth, and skin, and they become pigmented showing a characteristic red fluorescence in ultraviolet light. Hemolysis often occurs. This form of porphyria is not accompanied by lesions of the abdomen or nervous system.
Inborn errors of metabolism
Published in Angus Clarke, Alex Murray, Julian Sampson, Harper's Practical Genetic Counselling, 2019
The acute porphyrias form the most striking exception to the rule of recessive inheritance for most inborn errors due to enzyme defects. Acute intermittent porphyria, porphyria variegata, hereditary coproporphyria and protoporphyria all follow autosomal dominant inheritance. Careful investigation of urine and faecal porphyrins, enzyme studies and, where possible, molecular analysis are needed to exclude subclinical disease. Now that specific enzyme and gene defects are known, prenatal diagnosis may be possible but is rarely requested. The severe congenital erythropoietic porphyria follows autosomal recessive inheritance. Porphyria cutanea tarda, the most common of the group, is usually sporadic, with low recurrence risk for family members. This can be dominant or recessive. Much the commonest type is a ‘dominant’ disorder but of low penetrance and that requires adverse environmental factors such as alcoholic liver damage and/or homozygosity (or compound heterozygosity) for iron overload susceptibility variants in the haemochromatosis gene, HFE. Its common representation in textbooks as being inherited in a typically autosomal recessive fashion is misleading.
Sideroblastic Anemia and Porphyrias
Published in Harold R. Schumacher, William A. Rock, Sanford A. Stass, Handbook of Hematologic Pathology, 2019
Congenital erythropoietic porphyria is a very rare disorder transmitted as an autosomal recessive trait and caused by a defect in activity of uroporphyrinogen III synthase. The first sign of this disorder in infants is red urine that stains the diaper. Clinically, the disorder is characterized by photosensitivity, a cutaneous eruption following exposure to sunlight, and mutilation of nose, cartilage, and digits. There may also be hypertrichosis and erythrodontia, in which the teeth display red fluorescence under ultraviolet light, due to deposits of porphyrins in the dentin. Enlargement of the liver and spleen occurs. Treatment involves avoidance of sunlight and trauma to the skin. Suppression of erythropoiesis by hypertransfusion may also lead to amelioration of symptoms.
Porphyrias and photosensitivity: pathophysiology for the clinician
Published in Postgraduate Medicine, 2018
Loukas Kakoullis, Stylianos Louppides, Eleni Papachristodoulou, George Panos
Porphyrias manifest with either one or more of these clinical syndromes, depending of the substrates being accumulated. Acute intermittent porphyria (AIP) manifests as acute neurovisceral disease only, hereditary coproporphyria (HCP), and variegate porphyria (VP) combine acute neurovisceral disease with delayed blistering photosensitivity, whereas porphyria cutanea tarda (PCT) and congenital erythropoietic porphyria (CEP) manifest only as delayed blistering photosensitivity. However, it should be noted that photosensitivity in CEP is far more severe and can lead to photomutilation and disfigurement. Immediate and painful photosensitivity characterizes the two forms of protoporphyria, erythropoietic protoporphyria (EPP) and X-linked erythropoietic protoporphyria (XLEPP) [7,9,11]. Finally, an ultra-rare form of porphyria, ALA dehydratase deficiency porphyria (ALADP), manifests with acute neurovisceral disease, but due to the paucity of reported cases (less than 10 cases have been reported [7]), the complete range of its manifestations remains unknown [11], and thus will not be discussed. The main source of heme precursors in AIP, PCT, HCP, and VP is the liver, whereas the bone marrow produces the excess of porphyrins observed in CEP, EPP and XLEPP [7]. In hepatoerythropoietic porphyria, another ultra-rare form of porphyria, both the liver and bone marrow contribute to the excess production of heme precursors [12,13].
Givosiran, a novel treatment for acute hepatic porphyrias
Published in Expert Review of Precision Medicine and Drug Development, 2021
Manish Thapar, Sean Rudnick, Herbert L. Bonkovsky
The erythropoietic porphyrias comprise congenital erythropoietic porphyria (CEP), which is due to severe deficiency of uroporphyrinogen III synthase (URO3S) and erythropoietic protoporphyria (EPP), which is usually due to marked deficiency (<25% of normal) of FECH activity. However, about 10% of subjects with the clinical phenotype of EPP have gain-of-function mutations in ALA synthase-2 (the erythroid isoform), the gene for which resides on the X chromosome. Thus, this variant form is also known as X-linked protoporphyria (XLP).
Neurological and neuropsychiatric manifestations of porphyria
Published in International Journal of Neuroscience, 2019
Yiji Suh, Jason Gandhi, Omar Seyam, Wendy Jiang, Gunjan Joshi, Noel L. Smith, Sardar Ali Khan
Congenital erythropoietic porphyria (CEP) is the most rare type of porphyria which was first described by Schultz in 1874 in a 33-year-old man who excreted red urine containing hematoporphyrin [3–5]. In 1913, the photosensitizing properties of porphyrin were tested by Meyer-Betz by self-injecting hematoporphyrin into his vein. He observed photosensitizing lesions uncovered areas of his skin [6]. A study in 1895 by Stokvis revealed that rabbits died when they were injected with dark red urine that contained hematoporphyrin [6, 7].