Porphyrias Flashcards
Inheritance of acute intermittent porphyria
Autosomal dominant with incomplete penetrance; 80% of those who have it do not develop symptoms
Prevalence of acute intermittent porphyria
1/20,000
What enzyme deficiency causes acute intermittent porphyria?
50% function of porphobilinogen deaminase
What is the result of the enzyme deficiency in acute intermittent porphryia?
Buildup of ALA and porphobilinogen and low concentration of heme in the liver
Clinical impression of acute intermittent porphyria
Nerve damage that causes acute, intermittent attacks of abdominal pain, tachycardia, hypertension, muscle weakness, tremors, seizures, and psychiatric symptoms such as agitation and hallucinations
What is the mechanism of clinical presentation of acute intermittent porphyria?
Unknown
How does feedback worsen the disease?
Slightly lower production of heme causes lack of negative feedback inhibition of ALA synthase, which causes higher accumulation of ALA and porphobilinogen
Treatment of acute intermittent porphyria attacks
Glucose infusion and heme transfusion
Inheritance of variegate porphyria
Autosomal dominant with incomplete penetrance; almost none develop symptoms
Prevelance of variegate porphyria
1/100,000 in Finland; 1/333 in South African whites (due to founder effect)
Metabolite consequences of variegate porphyria
50% deficiency in protoporphyrinogen oxidase (enzyme #7), which leads to increased protoporphyrinogen III and coproporphyrinogen III in the liver. Heme is also reduced, leading to increased ALA and porphobilinogen
Cause of symptoms in variegate porphyria
Protoporphyrinogen and coproporphyrinogen are deposited in the skin, which is then converted to porphyrins by light and causes skin destruction; blistering and other skin lesions result
What drugs can induce ALA synthase activity, thereby worsening the symptoms of porphyrias?
Barbiturates, alcohol, steroids, and low-glucose diets
