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Hematology and oncology ` hematology and oncology—Pathology Hematology and oncology ` hematology and oncology—Pathology SectIon III 425
Heme synthesis, The porphyrias are hereditary or acquired conditions of defective heme synthesis that lead to the
porphyrias, and lead accumulation of heme precursors. Lead inhibits specific enzymes needed in heme synthesis,
poisoning leading to a similar condition.
condItIon aFFected enZyme accUmUlated SUBStRate PReSentIng SymPtomS
Lead poisoning Ferrochelatase and Protoporphyrin, ALA Microcytic anemia (basophilic stippling in
A ALA dehydratase (blood) peripheral smear A , ringed sideroblasts in
bone marrow), GI and kidney disease.
Children—exposure to lead paint mental
deterioration.
Adults—environmental exposure (eg, batteries,
ammunition) headache, memory loss,
demyelination (peripheral neuropathy).
Acute intermittent Porphobilinogen Porphobilinogen, ALA Symptoms (5 P’s):
porphyria deaminase, Painful abdomen
previously called Port wine–colored Pee
uroporphyrinogen I Polyneuropathy
synthase (autosomal Psychological disturbances
dominant mutation) Precipitated by drugs (eg, cytochrome P-450
inducers), alcohol, starvation
Treatment: hemin and glucose.
Porphyria cutanea Uroporphyrinogen Uroporphyrin (tea- Blistering cutaneous photosensitivity and
tarda decarboxylase colored urine) hyperpigmentation B .
Most common porphyria. Exacerbated with
B
alcohol consumption.
Causes: familial, hepatitis C.
Treatment: phlebotomy, sun avoidance,
antimalarials (eg, hydroxychloroquine).
Location Intermediates Enzymes Diseases
Glycine + succinyl-CoA
Mitochondria B – Glucose, hemin Aminolevulinic acid
6 synthase (rate-limiting step) Sideroblastic anemia (X-linked)
Aminolevulinic acid
Aminolevulinic acid
dehydratase Lead poisoning
Porphobilinogen
Porphobilinogen
deaminase Acute intermittent porphyria
Hydroxymethylbilane
Cytoplasm
Uroporphyrinogen III
Uroporphyrinogen
decarboxylase Porphyria cutanea tarda
Coproporphyrinogen III
Protoporphyrin
Mitochondria Fe 2+ Ferrochelatase Lead poisoning
Heme
↓ heme ↑ ALA synthase activity
↑ heme ↓ ALA synthase activity
FAS1_2019_10-HemaOncol.indd 425 11/7/19 5:05 PM
