Porphyria (ORPHA:738)
A group of rare hereditary metabolic diseases characterized by intermittent neurovisceral manifestations and/or skin lesions.
Epidemiology
Prevalence depends on the type of porphyria.
Clinical description
The group includes eight diseases with different manifestations. Symptoms mainly appear in adulthood, but some also affect children. Porphyrias can be classified into two groups, hepatic and erythropoietic, depending on the tissue predominantly affected by the metabolic abnormality. Clinical signs of hepatic porphyrias with cutaneous expression and erythropoietic porphyrias are bullous cutaneous lesions and/or acute pain in areas exposed to the sun (painful lesions). They are not associated with acute neurovisceral attacks. On the contrary, acute hepatic porphyrias can be associated with neurovisceral attacks manifested by intense abdominal pain (very often accompanied with nausea, vomiting and severe constipation), neurological disorders and mental disturbances. Two acute hepatic porphyrias (variegate porphyria and hereditary coproporphyria) can present with cutaneous photosensitivity as well.
Etiology
All porphyrias are caused by a deficiency or a gain-of-function in one of the enzymes involved in heme biosynthesis. These deficiencies or gains of function lead to an accumulation of porphyrins and/or their precursors (delta aminolevulinic acid, ALA, and porphobilinogen, PBG) in the liver or bone marrow. Precursors, and especially ALA, are responsible for neurological manifestations (direct or indirect neurotoxicity). The deficits or gains in enzyme function are the result of mutations of the coded corresponding genes.
Diagnostic methods
Diagnosis is essentially based on the measurement of porphyrins and their precursors in biological samples (urine, stools, blood).
Differential diagnosis
The differential diagnosis includes Guillain-Barré syndrome, and all causes of abdominal pain when the patient presents with acute pain, and photodermatoses when the patient presents with cutaneous symptoms.
Antenatal diagnosis
Antenatal diagnosis may be proposed for the families at risk of congenital erythropoietic porphyria and homozygous acute hepatic porphyrias.
Genetic counseling
Transmission of hereditary porphyrias is autosomal and either dominant with low penetrance or recessive with complete penetrance. One type of porphyria is X-linked dominant. The risk of transmitting the disease varies from 25% to 50%, depending on the type of porphyria. Penetrance varies from less than 2% to 100%, depending on the type of porphyria and the affected family members. Genetic counselling should be offered to affected families to identify individuals likely to develop or transmit the disease.
Management and treatment
Acute attacks must be considered as medical emergencies and treated by injection of human hemin and/or perfusion of carbohydrates. Cutaneous manifestations are mainly treated by phlebotomy and/or low-dose regimen of chloroquine.
Prognosis
Prognosis depends on the type of porphyria.

                            Last update: 
                            March 2024


                            - Expert reviewer(s): 
                            Dr Neila TALBI | MetabERN*


                                * European Reference Network