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PORPHYRIAS
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- 2. Porphyrias • Porphyriasare the metabolic disorders of heme synthesis, characterized by the increased excretion of porphyrins or porphyrin precurcors. • Porphyrias are either inherited or acquired. • The most common acquired form of porphyria is due to lead poisoning.
- 3. Classification of porphyrias Porphyrias Erythropoietic Hepatic • Erythropoietic (bone marrow): • Enzyme deficiency occurs in the erythrocytes. • Hepatic: • Enzyme defect lies in the liver.
- 4. Different types ofporphyrias Type of porphyria Enzyme defect Characteristics HEPATIC Acute intermittent porphyria Uroporphyrinogen I synthase Abdominal pain, neuropsychiatric symptoms Porphyria cutanea tarda Uroporphyrinogen decarboxylase Photosensitivity Hereditary coproporphyria Coproporphyrinogen oxidase Abdominal pain, Photosensitivity , neuropsychiatric symptoms Variegate porphyria Protoporphyrinogen oxidase Abdominal pain, Photosensitivity , neuropsychiatric symptoms ERYTHROPOIETIC PORPHYRIA Congenital erythropoietic porphyria Uroporphyrinogen III cosynthase Photosensitivity , increased hemolysis Protoporphyria Ferrochelatase Photosensitivity
- 5. Hepatic porphyria •Acute intermittent porphyria: • Enzyme defect: Uroporphyrinogen I synthase • Characteristic features: • Increased excretion of porphobilinogen & γ-ALA. • Urine gets darkened on exposure to air due to conversion of porphobilinogen to porphobilin & porphyrin. • It usually expressed after puberty.
- 6. Symptoms • Abdominalpain, vomiting & cardiovascular abnormalities. • Neuropsychiatric distrubances- due reduced activity of tryptophan pyrrolase (caused by depleted heme levels) resulting in the accumulation of tryptophan & 5- hydroxytryptamine.
- 7. • Symptoms aremore severe after administration of drugs (e.g. barbiturates) • It induce the synthesis of cytochrome P450. • This is due to the increased activity of ALA synthase causing accumulation of PBG & ALA. • These patients are not photosensitive. • It is treated by administration of hematin, it inhibits ALA sytnthase & accumulation of porphobilinogen.
- 8. Porphyria cutanea tarda • This is also known as cutaneous hepatic porphyria & is the most common porphyria. • It associated with liver damage caused by alcohol overconsumption or iron overload. • Enzyme deficiency: • Uroporphyrinogen decarboxylase.
- 9. Characteristic features •lncreased excretion of uroporphyrins (l & lll) & rarely porphobilinogen. • Cutaneous photosensitivity is the most important clinical manifestation of these patients. • Skin fragility, scarring, sclerodermoid skin changes. • Liver exhibits fluorescence due to high concentration of accumulated porphyrins.
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- 11. Hereditary coproporphyria •Enzyme defect: • Coproporphyrinogen oxidase. • Coproporphyrinogen lll & other intermediates (ALA and PBC) of heme synthesis prior to the blockade are excreted in urine & feces. • The patients are photosensitive.
- 12. Symptoms • Symptomsare similar to acute intermittent porphyria • Abdominal pain, vomiting & cardiovascular abnormalities.
- 13. • Neuropsychiatric distrubances-due reduced activity of tryptophan pyrrolase (caused by depleted heme levels) resulting in the accumulation of tryptophan & 5- hydroxytryptamine. • It is treated by administration of hematin, it inhibits ALA stnthase & accumulation of porphobilinogen.
- 14. Variegate porphyria •Enzyme defect: Protoporphyrinogen oxidase • Due to this blockade, protoporphyrin lX required for the ultimate synthesis of heme is not produced. • Almost all the intermediates (porphobilinogen, coproporphyrin, uroporphyrin, protoporphyrin etc.) of heme synthesis accumulate in the body & are excreted in urine and feces. • The urine of these patients is coloured & they exhibit photosensitivity
- 15. Erythropoietic porphyria •Congenital erythropoietic porphyria: • Enzyme defect: • Uroporphyrinogen III cosynthase. • Also caused by an imbalance between the activities of uroporphyrinogen I synthase and uroporphyrinogen lll cosynthase
- 16. Characteristic features •It is a rare congenital disorder. • Mostly contained in erythropoietic tissues (bone) • Individuals excrete uroporphyrinogen I & coproporphyrinogen I which oxidize respectively to uroporphyrin I & coproporphyrin I.
- 17. • The patientsare photosensitive (itching & burning of skin when exposed to light). • Skin pain or burning in sunlight • Erythema, swelling. • Erosions in light exposed areas-mainly in face & hands. • Scarring - shallow circular or linear. • Waxy thickening of the skin. • Increased hemolysis.
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- 19. Protoporphyria • Alsoknown as erythropoietic protoporphyria. • Enzyme defect: • Ferrochelatase. • Protoporphyrin IX accumulates in tissues & is excreted into urine & feces. • Reticulocytes (young RBC) & skin biopsy exhibit red flourorescence.
- 20. Acquired or toxicporphyria • It occur due to toxicity of several compounds. • Exposure of the body to heavy metals (e.g. lead), toxic compounds (hexachlorobenzene) and drugs (e.g. griseofulvin) inhibits many enzymes in heme synthesis. • These includes ALA dehydratase, uroporphyrin I synthase & ferrochelatase.
- 22. Reference Books •Text book of Biochemistry – U Satyanarayana • Text book of Biochemistry – DM Vasudevan • Text book of Biochemistry – MN Chatterjea
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