A 21 y.o. woman with a history of seizures comes to the ED with abdominal pain.
You notice her urine sitting on the counter.
Our patient had acute intermittent porphyria (AIP). This disease is caused by a deficiency of an enzyme of heme synthesis. It presents with neurovisceral symptoms including seizures, psychiatric manifestations, and abdominal pain. If the urine is allowed to stand outside the body, it gradually darkens due to breakdown of porphobilinogen into porphobilin and uroporphyrin causing a reddish brown color. There are several types of porphyria but basically they can be separated into two types: those with neurovisceral symptoms and those with cutaneous symptoms.
There are 8 steps in the pathway which can lead to overproduction of porphyrins. ALA is the rate limiting step. It can be induced by prolonged fasting or drugs like estrogen causing more heme to be produced by P450 pathway induction.
There is one carrier of AIP in every 2,000 people and it is autosomal dominant. The penetrance is incomplete however and only 2% of individuals with heme synthesis enzyme deficiencies manifest symptoms.
Elevated urine porphobilingen (PGB) confirms the diagnosis.
Porphyria cutanea tarda (PCT) is the most common type of porphyria. Rather than being a genetic defect; it is usually acquired. It presents with mainly skin manifestations: blistering and photosensitivity. 80 to 90% of patients with PCT have a history of heavy alcohol consumption because alcohol inhibits uroporphyrinogen decarboxylase leading to a build up of porphyrins. The porphyrins in the skin react with blue light in the skin releasing energy that is transferred to oxygen molecules oxidizing cell membrane lipids and causing blisters .The treatment involves treating the cause of the increased porphyrin: Fe overload, estrogen or viral infection.
porphyria cutanea tarda
Treatment of an acute attack of AIP includes treatment of abdominal pain, nausea and vomiting symptomatically. Dextrose is given because fasting can induce the liver to make more heme.( dextrose shuts down the drive for increasing ALA synthase) It is important to give hemin which limits porphyrin formation. More recently, givosiran an RNAi has been used. It can target 5- aminolevulinate synthase 1. Decreased ALAS1 means less ALA and less porphyrin.
Our patient was given 4 mg/kg of hemin in addition to symptomatic treatment. Her family was screened for AIP.
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Caballes F, Dendi H, Bonkovsky H. Hepatitis C, porphyria cutanea tarda and liver iron: an update. Liver Int. 2012 Apr 17;32(6):880-893.
Karp R, Wang B. Acute hepatic porphyria: expert guidance on diagnosis and management. ABIM MOC 12/16/2024. https://www.medscape.org/viewarticle/acute-hepatic-porphyria-expert-guidance-diagnosis-and-2024a1000n55/1