Heme Synthesis: Porphyrias

Question 1

Lead poisoning

Answer 1

interacts with zinc cofactor

• ALA dehydratase
• Ferrochetalase

ALA & protoporphyrin IX accumulate in urine
does not lead to photosensitivity

Question 2

Vitamin B6 deficiency

Answer 2

PLP needed as coenzyme for ALA synthase

heme synthesis cannot begin

Question 3

Acute Intermittent

Porphyria

Answer 3

deficiency of hydroxymethylbilane synthase

ALA and porphobilinogen in blood and urine

patients are NOT photosensitive

• dark purple color urine after 24 hours exposure to light and air
• severe abdominal pain
• highly agitated state
• respiratory problems

Triggers
- specific drugs, infections, ethanol abuse, abnormal estrogen metabolism

Treatment

• pain meds
• IV glucose, saline, hemin
• NO barbituates (stimulation of CYP450 can worsen situation > death)

Question 4

Congenital Erythropoietic Porphyria

Answer 4

Autosomal Recessive (erythroid cells, bone marrow)

uroporphyrinogen III synthase deficiency

uroporphyrin I and coproporphyrin I in tissues, blood & urine

MOST SEVERE photosensitivity 
severe damage to skin begining in childhood 
blisers, poor wound healing 
ulcers
infections
hypertichosis (excessive hair growth) 
Reddish-brown teeth 
"werewolf" features 

Bone Marrow Transplant

Question 5

Porphyria Cutanea Tarda

Answer 5

uroporphyrinogen decarboxylase deficiency

uroporphyrin III in tissues, blood, & urine
most common
patients are photosensitive

Type I (sporadic 80%)
Type II (familial, autosomal dominant 20%) 

Manifestations
- red urine
- cutaneous lesions
- accumulation of uroporphyrin in skin and liver l
erosions & bulbous lesions in sun exposed areas

can be triggered by liver damage (hepatitis, ethanol abuse)

avoidance of sun light alcohol & iron