Porphyrias

Views:
 
     
 

Presentation Description

No description available.

Comments

Presentation Transcript

Slide 1: 

An Overview - by Neha Mishra Porphyrias

Definition : 

Definition Inherited disorder Heme biosynthetic pathway

Basis of classification : 

Basis of classification Site Accumulation of porphyrins. PORPHYRIAS Erythropoietic Hepatic General Symptoms Neurologic Cutaneous Photosensitivity Reason Ecogenetic

Heme Biosynthesis : 

Heme Biosynthesis

Slide 5: 

Biosynthesis of Heme first and last 3 reactions take place in mitochondria - all others in cytoplasm - red blood cells have no mitochondria so can’t make heme formation of ?-aminolevulinic acid - all carbons from glycine and succinyl CoA - catalyzed by ALA synthase - requires pyridoxal phosphate - rate controlling step hemin formed from oxidation of heme not taken up by protein - hemin inhibits ALA synthase synthesis many drugs increase p450 synthesis, therefore decreasing heme - increases ALA synthase synthesis which increases ALA and heme synthesis

Slide 6: 

Biosynthesis of Heme Formation of porphobilinogen - dehydration of 2 ALA molecules - by ?-aminolevulinic acid dehydrase - cytoplasmic - very sensitive to lead and other heavy metals accounts, in part, for lead poisoning - increased ALA, anemia

Slide 7: 

Biosynthesis of Heme four porphobilinogens condensed to form uroporphyrinogen III 2 cytoplasmic enzymes: hydroxymethylbilane synthase uroporphyrinogen III synthase uroporphyrinogen II converted to coproporphyrinonogen III - transported back into mitochondria converted to protoporphyrinogen IX, then to protoporphyrin IX heme is formed by incorporation of iron (Fe+2) - partly spontaneous - ferrochelatase enhances rate - also inhibited by lead

Slide 8: 

HEPATIC PORTHYRIAS Increased plasma and urinary conc. of porphyrin precursors. 1. Acute Intermittent Porphyria Genetic Cause Uroporphyrinogen I Synthase Autosomal dominant Ecological Cause Gonadal Steroids Low calorie diet Clinical Features Abdominal pain CVS abnormalities Neuropsychiatric disorders.

HEPATIC PORTHYRIAS : 

HEPATIC PORTHYRIAS Increased plasma and urinary conc. of porphyrin precursors. Acute Intermittent Porphyria Porphyria Cutanea Tarda Hereditary Coproporphyria Variegate Porphyria

1. Acute Intermittent Porphyria : 

1. Acute Intermittent Porphyria Genetic Cause Uroporphyrinogen I Synthase Autosomal dominant Ecological Cause Gonadal Steroids Low calorie diet Clinical Features Abdominal pain CVS abnormalities Neuropsychiatric disorders.

2. Porphyria Cutanea Tarda : 

2. Porphyria Cutanea Tarda Genetic Cause Uroporphyrinogen decarboxylase Autosomal dominant Ecological Cause Excess Alcohol Iron overload Halogenated aromatic hydrocarbon Clinical Features Cutaneous photosensitivity Increased uroporphyrins I & III High risk of Hepatocellular carcinoma.

3. Hereditory Coproporphyria : 

3. Hereditory Coproporphyria Genetic Cause Coproporphyrinogen oxidase Autosomal dominant Clinical Features Increased coproporphyrinogen III & other intermidiates Same as AIP except Photosensitivity

4. Variegate Porphyria : 

4. Variegate Porphyria Genetic Cause Protoporphyrinogen oxidase Autosomal dominant trait Ecological Cause Same as AIP Clinical Features Increased in all intermidiates Photosensitivity Neurological symptoms

ERYTHROPOIETIC PORPHYRIAS : 

ERYTHROPOIETIC PORPHYRIAS Porphyrins from bonemarrow erythrocytes & plasma are deposited in the skin leading to cutaneous photosensitivity. Congenital Erythropoietic Porphyria Protoporphyria

1. Congenital Erythropoietic Porphyria : 

1. Congenital Erythropoietic Porphyria Gunther’s Disease Genetic Cause Uroporphyrinogen I Synthase & III cosynthase Autosomal recessive trait Clinical Features Increased UPG I & CPG I which oxidise to uroporphyrin and coproporphyrin (red pigments) Teeth : reddish brown Photosensitive Increased hemolysis

2. Protoporthyria : 

2. Protoporthyria Genetic Cause ferrochelatase Autosomal dominant trait Clinical Features Increased protoporphyrins. Skin manifestations differ from that of other porphyrias Recticulocytes & Skin biopsy exhibit red fluroscense

Diagnosis : 

Diagnosis DNA Diagnosis by mutation analysis is possible

Treatment : 

Treatment Hepatic Porphyria Heme therapy Phlebotomy Hydroxychloroquinone & chloroquinone Erythropoietic Porphyria Blood Transfusion Oral ß-Carotene improves tolerance to sunlight in many patients.

Thank you : 

Thank you contact: imsamyr@gmail.com

authorStream Live Help