Porphyria

Question 1

common symptoms of porphyria

Answer 1

• photosensitivity leading to skin blistering (porphyrin accumulation in skin)
• pale skin/skin discoloration
• reddish color
• neurologic symptoms (sleep disturbance, peripheral neuropathy)
• neuropsych symptoms
• abdominal pain, nausea/vomiting

Question 2

Acute intermittent porphyria pathophys

Answer 2

PBG deaminase mutation

Question 3

Porphyria attack triggers

Answer 3

• smoking
• alcohol
• sleep deprivation
• OCPs
• sulfonamides, AEDs

Question 4

Longer term sequela of porphyria

Answer 4

• HTN
• CKD/renal failure

Question 5

variegate porphyria 1) mechanism 2) ethnicity more common in

Answer 5

• Mutations in the PPOX gene. The PPOX gene makes a membrane bound mitochondrial enzyme called protoporphyrinogen oxidase,
• Dutch heritage

Question 6

Hereditary coproporphyria mechanism

Answer 6

• deficiency in coproporphyrogen oxidase

Question 7

Initial workup if concern for porphyria

Answer 7

urinary porphobilinogen (PBG) and total porphyrins

Question 8

AIP diagnosis 1) initial lab pattern consistent with AIP 2) confirmatory testing

Answer 8

Urinary PBG elevation
+ normal or slightly elevated total plasma porphyrins
+ normal or slightly increased stool porphyrins
confirmatory testing:
low erythrocyte PBGD activity (deficient enzyme in AIP but nonspecific finding in and of itself)
genetic testing

Question 9

Variegate porphyria 1) clinical features 2) country with highest prevalence

Answer 9

1) cutaneous blistering and/or acute neurovisceral attacks.
2) South Africa

Question 10

VP vs. AIP

Answer 10

1) Marked increase in stool porphyrins – Coproporphyrin III, protoporphyrin
2) plasma porphyrins are increased with a distinctive fluorescence peak at approximately 626 nm

Question 11

Distinguishing lab feature of hereditary coproporphyria

Answer 11

• significantly elevated level of fecal and urinary coproporphyrin, especially coproporphyrin III, during an acute attack, and often between attacks

Question 12

Porphyria management in general

Answer 12

1) Remove precipitant (eg stop drug, quit smoking)
2) Dextrose 500 gm daily (decreases heme synthesis)
3) Hemin 4 mg/kg for 4 days

Question 13

Monitoring required when giving hemin

Answer 13

1) DIC
2) Renal failure

Question 14

Newer treatment for porphyria + clinical benefit

Answer 14

• givosiran
• reduces frequency of porphyria attacks

Question 15

What porphyria patients need to do regularly

Answer 15

Avoid sun exposure

Question 16

What is the most common chronic porphyria?

Answer 16

porphyria cutanea tarda (PCT)

Question 17

porphyria cutanea tarda mechanism

Answer 17

Deficiency in enzyme called uroporphyrinogen III decarboxylase

Question 18

testable trigger for porphyria cutanea tarda

Answer 18

Hepatitis C

Question 19

porphyria cutanea tarda clinical features

Answer 19

• iron overload
  **cutaneous blistering

Question 20

porphyria cutanea tarda management

Answer 20

phlebotomy to remove iron (goal ferritin <50) or iron chelation

Question 21

porphyria cutanea tarda diagnosis

Answer 21

• elevated urine uroporphyrinogen

Question 22

congenital erythropoietic porphyria mechanism

Answer 22

• deficiency in uroporphyrin 3 synthase

Question 23

congenital erythropoietic porphyria management

Answer 23

• consideration of stem cell transplant
• transfusions

Question 24

Erythropoietic protoporphyria (EPP) 1) mechanism 2) clinical features

Answer 24

1) deficiency in ferrochelatase
2) severe photosensitivity, with exposure to sunlight causing painful skin reactions.
*not blistering

Question 25

1) Specific clinical features of AIP 2) porphyria symptom not seen

Answer 25

• *Neurologic symptoms are specific to AIP
  *no cutaneous symptoms

Question 26

porphyria cutanea tarda treatment

Answer 26

• phlebotomy
• low dose hydroxycholoroquine
• treat hep c if present

Question 27

EPP treatment

Answer 27

• afamelanotide
• beta carotene
• marrow transplantation

Question 28

Long term AIP complication

Answer 28

• paresis
• liver cancer
• renal failure

Question 29

Long term complications of PCT

Answer 29

• liver damage
• liver cancer

Question 30

AIP inheritance pattern

Answer 30

• autosomal dominant w/ LOW penetrance. So most people with gene actually never get sick.

Question 31

Role of liver transplant in AIP

Answer 31

• curative but reserved for patients with frequent attacks refractory to hemin

Question 32

EPP mutation

Answer 32

ferrochelatase (FECH)

Question 33

EPP inheritance

Answer 33

autosomal recessive

Question 34

EPP diagnosis

Answer 34

*Metal-free protoporphyrin (not complexed with Zn) - specific for EPP and XLP
- normal urine porphyrins

Question 35

EPP clinical features

Answer 35

• acute pain when exposed to light
• gallstones
• liver failure

Question 36

EPP treatment

Answer 36

• avoid sulnight
• Alpha-MSH receptor agonists - afamelanotide, dersimelagon
• preserve liver function

Question 37

How does hemin treat AIP?

Answer 37

• suppression of ALA (aminolevunic acid synthase) (ALA is upregulated due to deficiency of porphobilinogen deaminase)

Question 38

Increased labile iron pool seen in what

Answer 38

• states of iron overload