Group of eight inherited disorder of heme biosynthesis characterized by acute neurovisceral symptoms, skin lesions or both. Acute porphyrias present with severe abdominal pain, nausea, constipation, confusion, and seizure, and can be life-threatening. Cutaneous porphyrias present with either acute painful photosensitivity or skin fragility and blisters.
Acute Intermittent Porphyria; Hereditary Coproporphyria; Porphyria Variegata; ALAD Porphyria; Porphyria Cutanea Tarda; Congenital Erythropoietic Porphyria; Günther Disease; Hepato Erythropoietic Porphyria; Erythropoietic Protoporphyria; Doss Porphyria.
Large variation for each enzyme defect. Acute intermittent porphyria 1:20,000 in Europe, 1:10,000 in Sweden; porphyria variegate 1:250 to 1:500 in white South Africans; porphyria cutanea tarda 5 and 10:100,000; erythropoietic protoporphyria 1:35,000 live births.
See Tables P-2 and P-3. Porphyrias are grouped as acute hepatic porphyrias and photocutaneous porphyrias. Hepatic porphyrias are potentially life-threatening and can be triggered during anesthesia leading to an acute porphyric crisis. Photocutaneous porphyrias can also be triggered during anesthesia but are never life-threatening.
TABLE P-2Classification of the Inherited Human Porphyrias ||Download (.pdf) TABLE P-2 Classification of the Inherited Human Porphyrias
|Classification ||Inheritance ||Deficient Enzyme ||Symptoms |
|Acute Intermittent Porphyria ||Autosomal Dominant ||Porphobilinogen deaminase ||Neurologic |
|Hereditary Coproporphyria ||Autosomal Dominant ||Coproporphyrinogen oxidase ||Neurologic & Cutaneous |
|Porphyria Variegata ||Autosomal Dominant ||Protoporphyrinogen oxidase ||Neurologic & Cutaneous |
|ALAD Porphyria ||Autosomal Recessive ||Delta-aminolevulinic acid dehydratase ||Neurologic |
|Porphyria Cutanea Tarda ||Autosomal Dominant ||Uroporphyrinogen decarboxylase ||Cutaneous |
|Congenital Erythropoietic Porphyria (Günther Disease) ||Autosomal Recessive ||Uroporphyrinogen III synthetase ||Cutaneous & Hematologic |
|Hepato Erythropoietic Porphyria ||Autosomal Recessive ||Uroporphyrinogen decarboxylase ||Cutaneous & Hematologic |
|☞Erythropoietic Protoporphyria ||Autosomal Dominant ||Ferrochelatase ||Cutaneous |
TABLE P-3Pathophysiology of Porphyrias and Enzyme Defects ||Download (.pdf) TABLE P-3 Pathophysiology of Porphyrias and Enzyme Defects
|Enzyme Defect ||Heme Biosynthesis ||Form of Porphyria |
|Delta-Aminolevulinic Acid Synthase || |
Succinyl-CoA + Glycine
|ALAD Porphyria* |
|Delta-Aminolevulinic Acid Dehydrase || |
|Acute Intermittent Porphyria* |
|Uroporphyrinogen-III-Cosynthase Porphobilinogen Deaminase || |
|Congenital Erythropoietic Porphyria or Acute Intermittent Porphyria* |
|Uroporphyrinogen-III-Decarboxylase || |
|Porphyria Cutanea Tarda* or Hepato Erythropoietic Porphyria |
|Coproporphyrinogen-III-Oxidase || |
|Hereditary Coproporphyria* |
|Protoporphyrinogen Oxidase || |
|Porphyria Variegata* |
|Ferrochelatase || |
|Erythropoietic Porphyria |
| ||Heme || |
Inherited enzymatic defects of heme biosynthesis. The heme molecule is thereafter included in the biosynthesis of hemoproteins such as hemoglobin, myoglobin, microsomal cytochrome P450, peroxidase, and cyclooxygenase. Overproduction of specific heme precursors occurs upstream the characteristic enzymatic defect. This leads to increased baseline aminolevulinic acid (ALA) synthetase activity. The first and last three enzymes involved in heme synthesis are located in the mitochondria. The others are in the cytosol. Disease manifestations may be ...