Sections View Full Chapter Figures Tables Videos Annotate Full Chapter Figures Tables Videos Supplementary Content +++ PORPHYRIAS ++ Metabolic disorders of heme synthesis; may be hereditary or acquired Photosensitivity due to exposure of ultraviolet (UV) radiation in the Soret band (400–410 nm) +++ Classification of Porphyrias: Erythropoietic and Hepatic Forms (Based on the Primary Site of Expression of the Enzymatic Defect) ++ Nonacute porphyrias: porphyria cutanea tarda (PCT), erythropoietic porphyria (EPP), congenital erythropoietic porphyria (CEP), and hepatoerythropoietic porphyria (HEP); most common cutaneous manifestation is photosensitivity Acute porphyrias: acute intermittent porphyria (AIP), variegate porphyria (VP), hereditary coproporphyria (HCP), and δ-aminolevulinic acid (ALA) dehydratase deficiency porphyria (plumboporphyria) Heme biosynthesis Major sites of heme synthesis are bone marrow (85%) and in the liver Initial reaction takes place in the mitochondrion within the cell Condensation of 1-glycine and 1-succinylCoA by ALA synthase: this is the rate-limiting reaction of heme biosynthesis Mitochondrial ALA is transported to the cytosol ALA dehydratase (also called porphobilinogen synthase) dimerizes 2 molecules of ALA to produce porphobilinogen Uroporphyrinogen I synthase, also called porphobilinogen deaminase or PBG deaminase, causes condensation of 4 molecules of porphobilinogen to produce intermediate hydroxymethylbilane Hydroxymethylbilane undergoes enzymatic conversion to uroporphyrinogen III by uroporphyrinogen synthase plus a protein known as uroporphyrinogen III cosynthase In the cytosol, the acetate substituents of uroporphyrinogen (normal uroporphyrinogen III or abnormal uroporphyrinogen I) are decarboxylated by uroporphyrinogen decarboxylase (UROD) The resulting coproporphyrinogen III intermediate is transported to the interior of the mitochondrion, where, after decarboxylation, protoporphyrinogen IX results In the mitochondrion, protoporphyrinogen IX is converted to protoporphyrin IX by protoporphyrinogen IX oxidase Final reaction in heme synthesis takes place in the mitochondrion by ferrochelatase +++ ERYTHROPOIETIC PORPHYRIAS +++ Congenital Erythropoietic Porphyria (CEP) +++ GUNTHER DISEASE ++ Autosomal recessive with complete absence of uroporphyrinogen III synthase (UROS) gene activity; affects uroporphyrinogen III synthase and the production of uroporphyrinogen III Results in massive accumulation and excretion of uroporphyrin I and coproporphyrin I Clinical findings (appear soon after birth) Cutaneous: severe photosensitivity with burning, edema, bullae, mutilating scars, loss of brows/lashes, hypertrichosis, hyperpigmentation/hypopigmentation Ocular: photophobia, kerato conjunctivitis, ectropion, symblepharon, loss of vision Other: gallstones possible, cartilaginous breakdown, red/brown urine, erythrodontia (seen with Wood's lamp), splenomegaly, hemolytic anemia Laboratory findings Urine: uroporphyrin I, coproporphyrin I Stool: coproporphyrin I Blood: plasma-uroporphyrin I, coprophorphyrin I; red blood cell (RBC): uroporphyrin I, coproporphyrin, and some protoporphyrin Other diagnostic tests: urine fluoresces reddish pink Treatment: strict photoprotection, splenectomy, blood transfusions, activated charcoal, hydroxyruea, oral ascorbic acid, and α-tocopherol +++ Erythropoietic Protoporphyria (EPP) ++ Autosomal dominant, FECH gene mutation results in partial ferrochelatase deficiency Clinical findings Cutaneous (photosensitivity): painful erythematous, edematous plaques after exposure to UV light that may heal with scarring, skin lichenification, waxy, leathery pseudovesicles, and nail changes Hepatic: porphyrin gallstones (early age), liver disease (10% of patients): jaundice, cirrhosis Laboratory findings Urine: normal (protoporphyrin IX is not ... Your Access profile is currently affiliated with [InstitutionA] and is in the process of switching affiliations to [InstitutionB]. Please select how you would like to proceed. Keep the current affiliation with [InstitutionA] and continue with the Access profile sign in process Switch affiliation to [InstitutionB] and continue with the Access profile sign in process Get Free Access Through Your Institution Learn how to see if your library subscribes to McGraw Hill Medical products. Subscribe: Institutional or Individual Sign In Error: Incorrect UserName or Password Username Error: Please enter User Name Password Error: Please enter Password Sign in Forgot Password? Forgot Username? Download the Access App: iOS | Android Sign in via OpenAthens Sign in via Shibboleth You already have access! Please proceed to your institution's subscription. Create a free profile for additional features.