From the Guidelines
Porphyria is a group of rare inherited or acquired disorders that affect the production of heme, an essential component of hemoglobin in red blood cells, resulting from deficiencies in specific enzymes involved in the heme production pathway, leading to an accumulation of porphyrins or their precursors in the body. These disorders can be broadly categorized as acute (affecting the nervous system) or cutaneous (affecting the skin) 1. Symptoms vary widely depending on the type but can include severe abdominal pain, vomiting, constipation, muscle weakness, seizures, mental changes, sensitivity to sunlight, blistering of sun-exposed skin, and reddish-brown urine. The acute hepatic porphyrias (AHPs) include acute intermittent porphyria (AIP), variegate porphyria (VP), hereditary coproporphyria (HCP), and 5-aminolevulinic acid dehydratase deficiency porphyria (ALAD), which present with acute neurovisceral symptoms due to abnormal accumulation of the porphyrin precursors δ-aminolevulinic acid (ALA) and porphobilinogen (PBG) 1.
Key Characteristics of Porphyria
- Inherited disorders in the heme biosynthesis pathway
- Result from deficiencies in specific enzymes involved in the heme production pathway
- Accumulation of porphyrins or their precursors in the body
- Symptoms vary widely depending on the type
- Can be broadly categorized as acute (affecting the nervous system) or cutaneous (affecting the skin)
Diagnosis and Management
Diagnosis of AHPs is often missed, with a delay of more than 15 years from initial presentation, and the key to early diagnosis is to consider the diagnosis, especially in patients with recurring severe abdominal pain not ascribable to other causes 1. The key diagnostic test is a spot urine for ALA, PBG, porphyrins, and creatinine. Treatment of acute attacks should be with intravenous hemin given by peripherally inserted central catheter (PICC) line, and management often requires a multidisciplinary approach involving hematologists, neurologists, and dermatologists. Early diagnosis is crucial as some types can cause life-threatening complications if left untreated. Patients with recurrent attacks have a high chronic disease burden, including chronic nausea, fatigue, neuropathy, and kidney disease, and require ongoing monitoring and active management 1.
Long-term Complications
Patients with AHPs are at risk of chronic and long-term complications, including neuropathy, chronic kidney disease (CKD), hypertension, and hepatocellular carcinoma (HCC), and need for long-term monitoring 1. Quality of life is decreased considerably, with high rates of depression, anxiety, and insomnia. Patients on chronic hemin or givosiran require close follow-up for adverse effects and treatment response. Patients should be counseled on the chronic and long-term complications of AHP, including neuropathy, CKD, hypertension, and HCC, and need for long-term monitoring.
From the FDA Drug Label
PANHEMATIN therapy is intended to limit the rate of porphyria/heme biosynthesis possibly by inhibiting the enzyme δ-aminolevulinic acid synthetase 1 (ALAS1) About 50% of the women with acute intermittent porphyria experience an acute attack of porphyria in pregnancy and/or the puerperium.
Porphyria is a condition where the body has a problem with heme biosynthesis, but the exact definition of porphyria is not explicitly stated in the provided drug labels 2 2.
From the Research
Definition of Porphyria
- Porphyria is a group of uncommon metabolic diseases caused by enzyme deficiencies within heme biosynthesis that lead to neurotoxic or phototoxic heme precursor accumulation 3.
- Porphyrias are rare metabolic disorders, inherited or acquired, along the heme biosynthetic pathway, which could manifest with neurovisceral and/or cutaneous symptoms, depending on the defective enzyme 4.
- Porphyrias are inherited defects in heme metabolism that result in excessive secretion of porphyrins and porphyrin precursors 5.
Types of Porphyria
- There are four acute porphyrias characterized by neuropsychiatric symptoms: acute intermittent porphyria, variegate porphyria, hereditary coproporphyria, and 5-aminolevulinic acid dehydratase deficiency porphyria 3.
- Porphyrias can be classified into acute, (neuropsychiatric), cutaneous and mixed forms 5.
- There are seven main types of porphyrias; acute intermittent porphyria and plumboporphyria are predominantly neuropsychiatric; congenital erythropoietic porphyria, porphyria cutanea tarda and erythropoietic protoporphyria have predominantly cutaneous manifestations and hereditary coproporphyria and variegate porphyria are classified as mixed as they both have neuropsychiatric and cutaneous features 5.
Symptoms of Porphyria
- Neurovisceral porphyrias are characterized by acute attacks, in which excessive heme production is induced following exposure to a trigger, presenting with severe abdominal pain, vomiting, and tachycardia 4.
- Cutaneous symptoms are a consequence of elevated porphyrins in the blood stream, reacting to light and affecting sun-exposed areas, producing fragile erosive skin lesions in porphyria cutanea tarda (PCT) or non-scarring stinging and burning symptoms in erythropoietic protoporphyria (EPP) 4.
- Neurological complications usually result from severe episodes of acute attacks, including paralysis, hyponatremia, seizures, and coma 6.
- Acute attacks may also elicit neuropsychiatric symptoms such as confusion, hallucinations, anxiety, and psychosis 6.