Porphyrias
Porphyrias are a group of inborn errors of metabolism due to mutation in the genes directing the synthesis of heme . They are disorders in heme synthetic pathway due to deficiency of some enzymes in that pathway. They are characterized by excessive production in blood and excretion of formed porphyrins and their precursors mainly copropophyrins and uroporphyrins in urine. When acidic extracts of urine of patients having porphyria are exposed to U.V. light , red fluorescence is characteristic of the presence of these compounds in their urine. Porphyrias could be hereditary and familial and some are acquired but most forms of porphyrias in which there is over production of porphyrins have common clinical features.1- Photo sensitivity : sensitivity of skin to light because plasma porphyrins are in excess, they accumulate in skin. 2- Neurological signs : causing severe abdominal pain, vomiting, constipation امساك and often mental disturbances occur. Proper treatment of porphyria depends on laboratory investigation and accurate diagnosis. Some patients may develop anemia due to hemolysis.
Classification of porphyrias:
Several different classifications of porphyrias have been proposed. Porphyrias are classified according to whether excessive porphyrin production takes place in liver " hepatic porphyria " or in the bone marrow " erythropoietic porphyria " so they are classified into: 1- Hepatic porphyria. 2- Erythropoietic porphyria.1- Hepatic porphyrias. a- Intermittent acute porphyria It is due to partial deficiency of uroporphyrinogen synthetase enzyme leading to production of massive quantity of porphobilinogen and aminolevulinic acid in urine. No photo sensitivity in this condition because the deficiency is prior to the formation of porphyrins. b- Variegate porphyria : البورفيريا المبقعة It is an inherited deficiency in protoporphyrinogen oxidase enzyme and ferro chelatase leading to accumulation of amino levulinic acid, early porphyrinogen, uroporphyrinogen, coproporphyrinogen in urine and the patient has photo sensitivity and pigmented urine.
C- Hereditary coproporphyria : It is inherited partial deficiency of coproporphyrinogen oxidase enzyme leading to accumulation of coproporphyrinogen and uroporphyrinogen in urine . The symptoms are the same as acute intermittent porphyria but there is photosensitivity. There is limited capacity for the production of heme so aminoleulinic acid synthetase will be increased.
D- Porphyria cutanea tarda (slow moving or cutaneous hepatic porphyria) : It is the most common form of porphyria . It is either genetic or acquired associated with hepatic injury and secondary to liver disease. The genetic defect in the uroporphyrinogen decarboxylase enzyme deficiency leading to accumulation of uroporphyrins in the liver and urine. Patients with this type of porphyria, their liver has also fluorescence in UV light .
There is cutaneous photosensitivity . The acquired type is due to exposure to toxic compounds, such as lead, heavy metals, iron overload, hexochlorobenzene and alcohol.
2- Erythropoietic porphyria : It is believed that the metabolic abnormality is in the bone marrow. a- Congenital erythropoietic porphyria ( pink tooth disease ) : It is due to the deficiency of uroporphyrinogen III cosynthetase enzyme , so that the ratio of uroporphyrinogen I synthatase to uroporphyrinogen III cosynthetase is about 100:1. There is photosensitivity and hemolysis and hemolytic anemia might develop in these patients. b- Erythropoietic protoporphyria : It is caused by reduced activity of ferrochelatase enzyme, so, large amounts of protoporphyrines are formed in the circulation, in the urine and in feces. There is photosensitivity and urticaria on exposure to sunlight.