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890 Part VI: The Erythrocyte Chapter 58: The Porphyrias 891

Mitochondrion
H 2 C
Glycine + H 3 C Fe
succinyl-CoA
ALAS B FECH Protoporphyrin IX
N CH 3
SA H 2 C A N Fe N C PPO
δ -Aminolevulinic acid EPP VP
H 3 C N
D Protoporphyrinogen IX
H 3 C
HCP
Heme Coproporphyrinogen III
CPO
δ -Aminolevulinic acid

ALAD ADP Coproporphyrinogen III
PCT
UROD
Porphobilinogen
AIP CEP Uroporphyrinogen III
PBGD Hydroxymethylbilane UROS Coproporphyrinogen I

Nonenzymatic UROD
Uroporphyrinogen I
Cytosol

Figure 58–1. Enzymes and intermediates in the heme biosynthetic pathway and the type of porphyria associated with a deficiency of each
enzyme (indicated by Ø). Gain-of-function mutation of the erythroid form of ALA synthase is not shown. ADP, ALA dehydratase porphyria; AIP, acute
intermittent porphyria; ALA, δ-aminolevulinic acid; ALAD, δ-aminolevulinic acid dehydratase; ALAS, δ-aminolevulinic acid synthase; CEP, congenital
erythropoietic porphyria; CoA, coenzyme A; CPO, coproporphyrinogen oxidase; EPP, erythropoietic protoporphyria; FECH, ferrochelatase; HCP, heredi-
tary coproporphyria; PBG, porphobilinogen; PBGD, porphobilinogen deaminase; PCT, porphyria cutanea tarda; PPO, protoporphyrinogen oxidase; SA,
sideroblastic anemia; UROD, uroporphyrinogen decarboxylase; UROS, uroporphyrinogen III synthase; VP, variegate porphyria.

TABLE 58–2. Biochemical Findings Including Major Increases in Porphyrins and Porphyrin Precursors in the Human
Porphyrias
Porphyria Erythrocytes Plasma Urine Stool
XLP Metal-free and zinc Protoporphyrin (∼634 nm) ‡ ¶ Protoporphyrin *
protoporphyrin §
ADP Zinc protoporphyrin ALA * ALA, coproporphyrin III *
AIP Decreased PBGD activity ALA, PBG (∼620 nm, some ALA, PBG, uroporphyrin *
*
(most cases) * cases) †
CEP Uroporphyrin I; copro- Uroporphyrin I, coproporphy- Uroporphyrin I; coproporphyrin I Coproporphyrin I
porphyrin I rin I (∼620 nm) †
PCT and HEP Zinc protoporphyrin (in Uroporphyrin, heptacarboxyl Uroporphyrin, heptacarboxyl Heptacarboxyl porphyrin,
HEP) porphyrin (∼620 nm) † porphyrin isocoproporphyrins
HCP * ‡ (∼620 nm, some cases) † ALA, PBG, coproporphyrin III Coproporphyrin III
VP * Protoporphyrin (∼628 nm) † ALA, PBG, coproporphyrin III Coproporphyrin III,
protoporphyrin
EPP Metal-free Protoporphyrin (∼634 nm) † ¶ Protoporphyrin *
protoporphyrin §
ADP, δ-aminolevulinate dehydratase deficiency porphyria; AIP, acute intermittent porphyria; ALA, δ-aminolevulinic acid; CEP, congenital ery-
thropoietic porphyria; EPP, erythropoietic protoporphyria; HCP, hereditary coproporphyria; HEP, hepatoerythropoietic porphyria; PBG, porpho-
bilinogen; PCT, porphyria cutanea tarda; VP, variegate porphyria; XLP, X-linked protoporphyria.
*Porphyrin levels normal or slightly increased.
† Fluorescence emission peak of diluted plasma at neutral pH.
‡ Plasma porphyrins usually normal, but increased when blistering skin lesions develop.
§ Zinc protoporphyrin ≤15 percent of total in EPP, but 15 to 50 percent in XLP.
¶ Increase in urine porphyrins (especially coproporphyrin) only with hepatopathy.

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