Porphyria Flashcards
common symptoms of porphyria
- 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
Acute intermittent porphyria pathophys
PBG deaminase mutation
Porphyria attack triggers
- smoking
- alcohol
- sleep deprivation
- OCPs
- sulfonamides, AEDs
Longer term sequela of porphyria
- HTN
- CKD/renal failure
variegate porphyria 1) mechanism 2) ethnicity more common in
- Mutations in the PPOX gene. The PPOX gene makes a membrane bound mitochondrial enzyme called protoporphyrinogen oxidase,
- Dutch heritage
Hereditary coproporphyria mechanism
- deficiency in coproporphyrogen oxidase
Initial workup if concern for porphyria
urinary porphobilinogen (PBG) and total porphyrins
AIP diagnosis 1) initial lab pattern consistent with AIP 2) confirmatory testing
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
Variegate porphyria 1) clinical features 2) country with highest prevalence
1) cutaneous blistering and/or acute neurovisceral attacks.
2) South Africa
VP vs. AIP
1) Marked increase in stool porphyrins – Coproporphyrin III, protoporphyrin
2) plasma porphyrins are increased with a distinctive fluorescence peak at approximately 626 nm
Distinguishing lab feature of hereditary coproporphyria
- significantly elevated level of fecal and urinary coproporphyrin, especially coproporphyrin III, during an acute attack, and often between attacks
Porphyria management in general
1) Remove precipitant (eg stop drug, quit smoking)
2) Dextrose 500 gm daily (decreases heme synthesis)
3) Hemin 4 mg/kg for 4 days
Monitoring required when giving hemin
1) DIC
2) Renal failure
Newer treatment for porphyria + clinical benefit
- givosiran
- reduces frequency of porphyria attacks
What porphyria patients need to do regularly
Avoid sun exposure
What is the most common chronic porphyria?
porphyria cutanea tarda (PCT)
porphyria cutanea tarda mechanism
Deficiency in enzyme called uroporphyrinogen III decarboxylase
testable trigger for porphyria cutanea tarda
Hepatitis C
porphyria cutanea tarda clinical features
- iron overload
**cutaneous blistering
porphyria cutanea tarda management
phlebotomy to remove iron (goal ferritin <50) or iron chelation
porphyria cutanea tarda diagnosis
- elevated urine uroporphyrinogen
congenital erythropoietic porphyria mechanism
- deficiency in uroporphyrin 3 synthase
congenital erythropoietic porphyria management
- consideration of stem cell transplant
- transfusions
Erythropoietic protoporphyria (EPP) 1) mechanism 2) clinical features
1) deficiency in ferrochelatase
2) severe photosensitivity, with exposure to sunlight causing painful skin reactions.
*not blistering
1) Specific clinical features of AIP 2) porphyria symptom not seen
- *Neurologic symptoms are specific to AIP
*no cutaneous symptoms
porphyria cutanea tarda treatment
- phlebotomy
- low dose hydroxycholoroquine
- treat hep c if present
EPP treatment
- afamelanotide
- beta carotene
- marrow transplantation
Long term AIP complication
- paresis
- liver cancer
- renal failure
Long term complications of PCT
- liver damage
- liver cancer
AIP inheritance pattern
- autosomal dominant w/ LOW penetrance. So most people with gene actually never get sick.
Role of liver transplant in AIP
- curative but reserved for patients with frequent attacks refractory to hemin
EPP mutation
ferrochelatase (FECH)
EPP inheritance
autosomal recessive
EPP diagnosis
*Metal-free protoporphyrin (not complexed with Zn) - specific for EPP and XLP
- normal urine porphyrins
EPP clinical features
- acute pain when exposed to light
- gallstones
- liver failure
EPP treatment
- avoid sulnight
- Alpha-MSH receptor agonists - afamelanotide, dersimelagon
- preserve liver function
How does hemin treat AIP?
- suppression of ALA (aminolevunic acid synthase) (ALA is upregulated due to deficiency of porphobilinogen deaminase)
Increased labile iron pool seen in what
- states of iron overload
