group of metabolic disorders from enzyme deficiency in heme synthesis.
Location of heme synthesis
occurs in liver and bone marrow 20/80
What is the rate limiting step in hepatic synth
What effects heme production
Heme production is inhibited by heme end product and induced by stimulators of the CPY450 pathway.
What are the two forms of porphyria
acute and cutaneous
What is the predominant site of porphyria
Acute porphyria SX
abd pain, tachycardia, dark urine. Peripheral sensory deficits and weakness leading to ascending paralysis or quadriplegia
Acute porphyria neuropsychiatric SX
hysteria, depression, psychosis, confusion, hallucinations, seizures, coma
Causes of acute porphyria
overproduction of ALA and PBG (PBG neurotoxic)
Epidem of acute porphyria
5 X more likely in F than in M. Caused by drugs, alcohol, smoking, steroids, sex hormones, meds stimulate CP450. Fasting, infxns, pregnacy. Clincally latent in 65-80%
Acute intermittent porphyria
most common acute porphyria. Mainly manifests as derangement in ANS or psychiatric disorder.
Cause of AIP
partial deficiency of PBG deaminase. Autosomal dominant w/ variable expression.
AIP common SX
abd pain, vomiting, consitpaton, muscle weakness, mental symptoms, limb, head/neck chest pain, tachycardia, etc.
Acute porphyrias types
ALA dehydratase deficiency (rare) [AR w/ lrg amts of ALA in urine], hereditary coproporphyria, variegate porphyria (both AD w/ variable expression, both have neuro sx w/ cutaneous lesions]
Treatment of acute porphyrias
Intravenous fluids, glucose admin, IV hematin. Avoidance of precipitants. Acute porph trig by menses imrpoved w/ oral contr pill. Screen for hepatocellular carcinoma. Use special sunscreen that protects
Most common porphyria
Porphyria cutanea tarda
Porphyria cutanea tarda cause
deficiency activity of uroporphyrinogen decarboxylase. 20% heteroz UROD mutation or AD w/ low penetrance
when does Porphyria cutanea tarda present
mid to late life.
what causes Porphyria cutanea tarda manifestation
when hepatic UROD inhibited & activity below 20% normal.
Porphyria cutanea tarda causes
factors/ diseases that contrib to iron accumulation or oxid stress in hepatocytes, excessive alc conspmtn, estrogen use, chronic HCV, hepatic siderosis, HIV, smoking, end stage renaldisease, myeloproliferative disorders
phlebotomy (blood letting) 1U (450 mL) every 2 weeks until ferritin below 20ng/ mL. If no response, target ferritin not reached or incorrect dx. Repeat tx w/ relapses. Also low dose hydroxychloroquine or chloroquine. Avoid causes
Hepatoerythropoietic porphria (HEP) cause
UROD deficiency, AR form of familial PCT. Rare, more severe, resembles congenital erythropoietic porphyria.
when does HEP present
childhood (before 2 yrs old)
Congenital erythropoietic porphyria cause
AR uroporphyrinogen III cosynthase defect.
Congenital erythropoietic porphyria SX
presents 1st yr of life, blisters, disfiguring lesions in exposed areas, erythrodontia (brown teeth), splenomegaly
Congenital erythropoietic porphyria tests
coombs test (negative result), hemolytic anemia
Congenital erythropoietic porphyria treatment
splenectomy, xfusion/ hematin infusion, BMT curative if severe patient
Erythropoietic protoporphyria (EPP)patho
partial deficiency of ferrochelatase which final step in heme synth, 2nd most common, AD w/ variable penetrance.