Porphyria Flashcards
Define porphyria.
Genetic or acquired conditions that affect heme metabolism leading to accumlation of heme precursors, for example lead inhibits specific heme metabolism enzymes leading to acquired porpyhria.
Explain the biochemical pathway involved in heme metabolism.
Explain lead poisoning.
Descibe acute intermittent porphyria.
Autosomal dominant with reduced penetrance
- More common in women
- Can cause fever, hypertension, tachycardia, respiratory failure which can be fatal
- No photosensitivity!
- Porphorobilinogen and ALA are neurotoxic, ALA inhibits GABA
- A very important finding is that urine is orange which turns dark brown when left to oxidise in air, due to the presence of porphrobilinogen and ALA in urine.
Explain prophyria cutanea tarda.
- Most responsive to therapy, begins in adulthood.
- Photosensitivity.
- Liver function tests are normal
- Treatment includes withdrawing offending agents and phlebotomy Inhibits hepatic enzymes so it is precipitated by
- Hep C
- Hemachromatosis
- Alcohol
- Smoking
- Estrogen rxn
- Polychlorinated cyclic hydrocarbon exposure
Explain the heme biosynthetic pathway as shown in this lecture.
How are different kinds of porphria classified?
Classified into 2 groups; acute neurologic attacks or chronic cutaneous photosensitivity. It involves the following diseases.
What disease are classified undererythropoietic cutaneous porphyria?What are their common features?
- Involved erythropoietic protoporphyria (EPP) and congenital erythropoietic porphyria (CEP).
- Associated with increased prophyrins in bone marrow
- Presents with cutaneous photosensitivity in utero or early childhood, other porphyrias present in adulthood.
Explain EPP
Erythropoietic protoporphyria (EPP)
* Third most common porphyria overall, most common childhood porphyria – Usual onset before age 10
* Sun exposure causes pain, redness, edema & itching w/in minutes – Less blistering & scarring than other cutaneous porphyrias
Autosomal recessive deficiency of ferrochelatase – Only 10% with deficiency develop symptoms
* Protoporphyrin accumulates in RBCs, diffuses into plasma, enters skin, cleared by liver & secreted in bile
* Increased risk of hemolytic anemia, gallstones, liver disease
* RBC protoporphyrin increased (absent in urine)
Treatment: IV heme therapy, plasmapheresis and avoid sun exposure.
Explain CEP.
Congenital Erythropoietic Porphyria (CEP)
* AKA Gunther’s Disease
* Associated with vampire folklore
* Autosomal recessive with onset during infancy
* Mutilating photodermatitis with scarring & erythrodontia
* Hemolytic anemia of newborn
* Uroporphyrinogen III cosynthase deficiency – uroporphyrinogen I oxidized to uroporphyrin & excreted into urine
Treatment: protection from sun, transfusion for anemia and stem cell transplantation.
What diseases are involved in acute neurologic porphyrias?What are their common features?
- Symptoms of acute attack are nonspecific & seen in other diseases
- All but AIP and ALAD have photosensitivity PBG almost always increased in AIP, VP & HCP but not in other diseases
Explain Variegate Porphyria.
- Acute neurological symtpoms - Abdominal pain, neuropathic and psychiatric
- Photosensitivity leads to cutaneous lesions
- Autosomal dominant inheritance – PPOX gene -> Protoporphyrinogen oxidase deficiency
- Urine PBG & ALA elevated (maybe normal between attacks)
- Fecal protoporphyrin & coproporphyrin >2X ↑ – Remain elevated between attacks
Explain hereditary coproporphyria (HCP).
- One of rarest forms of porphyria
- Autosomal dominant inheritance
- Presents after onset of puberty
- Acute neuropathic presentation – Clinically indistinguishable from AIP & VP
- Photosensitivity in 33% cases like PCT & VP
- Deficiency of coproporphyrinogen oxidase
- Hallmark is ↑ coproporphyria in urine & feces similar to VP
- Fecal porphyrins differentiate HCP from VP & AIP – HCP has coproporphyrin III:I ratio of 10-20 with no elevation of protoporphyrin
Explain ALAD deficiency.
- Extremely rare form of acute neurologic porphyria
- Only acute porphyria to begin in childhood
- Abdominal pain, vomiting, pain in extremities
- No photosensitivity
- Autosomal recessive inheritance
- Aminolevulinic acid dehydratase deficiency Significantly elevated urine ALA level
How do we treat acute porphyrias?
Withdraw offending agent and IV hemin therapy, it works by inhibiting ALA synthase activity, this is the first and rate limiting step in biosynthesis of heme.
