Inherited disorder of heme biosynthesis.
++ Table Graphic Jump Location Table P-2 Classification of the Inherited Human Porphyrias ||Download (.pdf)
Table P-2 Classification of the Inherited Human Porphyrias
|Acute Intermittent Porphyria||Autos D||Porphobilinogen deaminase||Neurologic|
|Hereditary Coproporphyria (HC)||Autos D||Coproporphyrinogen oxidase||Neuro + Cut|
|Variegate Porphyria (VP)||Autos D||Protoporphyrinogen oxidase||Neuro + Cut|
|Doss Porphyria (DP)||Autos R||ALA dehydratase||Neurologic|
|Porphyria Cutanea Tarda (PCT)||Autos D||Uroporphyrinogen decarboxylase||Cutaneous|
|Günther Disease or Congenital Erythropoietic Porphyria (CEP)||Autos R||Uroporphyrinogen III synthetase||Cut + Hemato|
|Hepato Erythropoietic Porphyria (HEP)||Autos R||Uroporphyrinogen decarboxylase||Cut + Hemato|
|Erythropoietic Protoporphyria (EPP)||Autos D||Ferrochelatase||Cutaneous |
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. They are classified as erythropoietic or hepatic depending
on the primary organ in which excess production of porphyrins or precursors
occurs (see Table P-2).
Acute intermittent porphyria (AIP) 1:20,000 in Europe,
1:10,000 in Sweden; variegate porphyria (VP) 1:250 to 1:500 in white South
Africans; erythropoietic protoporphyria (EPP) 1:35,000 live births.
See the classification Table P-2.
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 a result of
increased ALA synthetase activity, increased porphyrin accumulation, or
decreased heme production. Porphyrins are highly reactive oxidants, and skin
accumulation causes photosensitivity. Neuronal damage throughout the central
and peripheral nervous system also occurs, though the mechanism of this
severe neuropathy is unknown. See Table P-3.
++ Table Graphic Jump Location Table P-3 Pathophysiology of Porphyrias and Enzyme Defects ||Download (.pdf)
Table P-3 Pathophysiology of Porphyrias and Enzyme Defects
Difficult in the latent stage, but diagnosis is possible
by DNA analysis. The presence of urine that becomes dark or
port-wine reddish color after staying should prompt a diagnosis workup. During a
porphyric crisis, measurement of urine porphyrin and porphyrinogen
precursors is indicated and will confirm the diagnosis.
Acute attacks occur in AIP, hereditary coproporphyria (HCP), VP, and Doss porphyria
(DP). These attacks are often triggered by certain drugs, although these drugs (see Pharmacological Implications and Table P-4 below) do not always trigger attacks, as well
as by fasting, alcohol intake, or infection. Although hepatic porphyrias are rarely
symptomatic before puberty, latent carriers such as prepubertal ...