From the Guidelines
Variegate Porphyrias (VP) are a type of acute Porphyria characterized by inherited disorders in the heme biosynthesis pathway, resulting in acute neurovisceral symptoms due to abnormal accumulation of porphyrin precursors.
Key Characteristics of Variegate Porphyrias
- Inherited disorder: VP is an autosomal dominant disorder, meaning a single copy of the mutated gene is enough to cause the condition 1, 2.
- Heme biosynthesis pathway: VP is caused by mutations in the protoporphyrinogen oxidase (PPOX) gene, leading to a deficiency in the enzyme responsible for converting protoporphyrinogen to protoporphyrin 1, 3.
- Acute neurovisceral symptoms: VP presents with severe acute abdominal pain, nausea, vomiting, constipation, muscle weakness, neuropathy, tachycardia, and hypertension 1, 2.
- Porphyrin precursors: The accumulation of δ-aminolevulinic acid (ALA) and porphobilinogen (PBG) is responsible for the symptoms of VP 1, 2.
Diagnosis and Management of Variegate Porphyrias
- Screening tests: Random urine porphobilinogen and δ-aminolevulinic acid corrected to creatinine are the screening tests of choice for VP 2.
- Genetic testing: Genetic testing for pathogenic variants in the PPOX gene can confirm the diagnosis of VP 1, 2.
- Treatment: The cornerstones of management include discontinuation of porphyrinogenic drugs and chemicals, administration of oral or intravenous dextrose and intravenous hemin, and use of analgesics and antiemetics 2.
- Prophylactic therapy: Patients with recurrent acute attacks (4 or more per year) should be considered for prophylactic therapy with intravenous hemin or subcutaneous givosiran 2.
From the Research
Definition and Characteristics of Variegate Porphyrias (VP)
- Variegate Porphyria (VP) is one of the hepatic porphyrias that results from the deficiency of protoporphyrinogen oxidase, an enzyme in the heme synthesis pathway 4, 5, 6, 7.
- The name porphyria variegata refers to its many presentations, which include various neuropsychiatric and cutaneous manifestations 4.
- VP is an autosomal dominant inherited trait resulting in decreased activity of protoporphyrinogen oxidase 5.
Clinical Presentations
- Emergency department (ED) presentations due to VP are most commonly neuropathic abdominal pain 4.
- The disease is characterized clinically by photosensitive skin disease and a propensity to acute neurovisceral crises 5.
- Acute attacks of variegate porphyria appear to be less easily provoked and to be milder than those associated with acute intermittent porphyria 5.
Diagnosis and Treatment
- The gene for human protoporphyrinogen oxidase has been identified and sequenced, and several mutations in the protoporphyrinogen oxidase gene sequence have been identified 5.
- A specific plasma fluorometric emission at 626 nm has been shown in VP patients, but this method is specific but poorly sensitive, especially in detection of asymptomatic carriers 8.
- Intravenous dextrose and heme administration remain the first-line treatment for abdominal pain attributable to known acute hepatic porphyria attacks 4.
- Liver transplantation is also a possible treatment option for variegate porphyria, as it can lead to recovery from the disease 7.