Porphyria (Acute) Testing Algorithm*

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Porphyria (Acute) Testing Algorithm* Symptoms: ■ Neurovisceral attacks (abdominal pain, neuropathy, psychiatric symptoms) ■ Tachycardia and hypertension Possible acute porphyria: ■ Acute intermittent porphyria (AIP) ■ Variegate porphyria (VP)a ■ Hereditary coproporphyria (HCP)b ■ Aminolevulinic acid dehydratase de ciency porphyria (ADP) Excludes acute YES porphyrias ■ PQNRU / Porphyrins, Quantitative, Normal results-were samples Isolated ALA increase Random, Urinec collected during an acute episode? Includes porphobilinogen NO ■ PBALP / Porphobilinogen and To differentiate ADP from tyrosinemia type I and heavy metal Aminolevulinic Acid, Plasmad Retest during acute episode intoxication order: ■ ALAD / Aminolevulinic Acid Dehydratase (ALAD), Whole Bloode ■ OAU / Organic Acids Screen, Urine ■ HMCRU / Heavy Metal/Creatinine Ratio, with Re ex, Urine Increased porphobilinogen, possible increases OR in uroporphyrin, coproporphyrin, and/or ALA ■ HMDB / Heavy Metals Screen with Demographics, Blood Decreased ALAD activity Normal ALAD activity Perform: ■ PBGD_ / Porphobilinogen Deaminase (PBGD), Whole Bloodf ■ FQPPS / Porphyrins, Feces Confirms ADP Excludes ADP a. 80% of patients with VP have cutaneous symptoms b. 20% of patients with HCP have Decreased Increased coproporphyrin Increased coproporphyrin Normal PBGD activity and cutaneous symptoms PBGD activity III/I ratio (<10) and III/I ratio (>10) and fecal porphyrin profile c. Specimens collected during symptomatic period will be most protoporphyrin coproporphyrin III informative d. Plasma specimen for those unable to give urine AIP – Family studies VP – Family studies HCP – Family studies ■ Excludes VP and HCP e. ALAD test is not useful for lead may be warranted may be warranted may be warranted ■ AIP not excludedg intoxication cases f. 5% of AIP patients have normal PBGD activity in erythrocytes g. Specimens collected during HMBSZ / HMBS Gene, PPOXZ / PPOX Gene, CPOXZ / CPOX Gene, asymptomatic period will be most Full Gene Analysis, Varies Full Gene Analysis, Varies Full Gene Analysis, Varies informative. * Interpretive report provided for all tests in this algorithm © Mayo Foundation for Medical Education and Research (MFMER). All rights reserved. 10/2019.

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Hyperbilirubinemia
Porphyrins Porphyrins (Porphins) are cyclic tetrapyrol compounds formed by the linkage )). of four pyrrole rings through methenyl bridges (( HC In the reduced porphyrins (Porphyrinogens) the linkage of four pyrrole rings (tetrapyrol) through methylene bridges (( CH2 )) The characteristic property of porphyrins is the formation of complexes with the metal ion bound to nitrogen atoms of the pyrrole rings. e.g. Heme (iron porphyrin). Proteins which contain heme ((hemoproteins)) are widely distributed e.g. Hemoglobin, Myoglobin, Cytochromes, Catalase & Tryptophan pyrrolase. Natural porphyrins have substituent side chains on the eight hydrogen atoms numbered on the pyrrole rings. These side chains are: CH 1-Methyl-group (M)… (( 3 )) 2-Acetate-group (A)… (( CH2COOH )) 3-Propionate-group (P)… (( CH2CH2COOH )) 4-Vinyl-group (V)… (( CH CH2 )) Porphyrins with asymmetric arrangement of the side chains are classified as type III porphyrins while those with symmetric arrangement of the side chains are classified as type I porphyrins. Only types I & III are present in nature & type III series is more important because it includes heme. 1 Heme Biosynthesis Heme biosynthesis occurs through the following steps: 1-The starting reaction is the condensation between succinyl-CoA ((derived from citric acid cycle in the mitochondria)) & glycine, this reaction is a rate limiting reaction in the hepatic heme synthesis, it occurs in the mitochondria & is catalyzed by ALA synthase (Aminolevulinate synthase) enzyme in the presence of pyridoxal phosphate as a cofactor. The product of this reaction is α-amino-β-ketoadipate which is rapidly decarboxylated to form δ-aminolevulinate (ALA). 2-In the cytoplasm condensation reaction between two molecules of ALA is catalyzed by ALA dehydratase enzyme to form two molecules of water & one 2 molecule of porphobilinogen (PBG) which is a precursor of pyrrole.
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