Porphyria
Porphyria refers to a group of disorders caused by abnormalities in the chemical steps that lead to heme production, which can affect the skin or the nervous system.
Overview
Porphyria is a group of disorders caused by abnormalities in the chemical steps that lead to heme production. Heme is a vital molecule for all of the body's organs, most abundant in the blood, bone marrow, and liver. It is a component of several iron-containing proteins, including hemoglobin.
Types of Porphyria
Cutaneous Porphyrias
These primarily affect the skin. Areas exposed to the sun become fragile and blistered, which can lead to infection, scarring, changes in skin coloring, and increased hair growth. Examples include:
- Congenital erythropoietic porphyria
- Erythropoietic protoporphyria
- Hepatoerythropoietic porphyria
- Porphyria cutanea tarda
Acute Porphyrias
These primarily affect the nervous system. Signs and symptoms appear quickly and include abdominal pain, vomiting, constipation, diarrhea, muscle weakness, seizures, fever, and mental changes such as anxiety and hallucinations. Examples include:
- Acute intermittent porphyria
- ALAD deficiency porphyria
- Hereditary coproporphyria (can have both acute and cutaneous symptoms)
- Variegate porphyria (can have both acute and cutaneous symptoms)
Causes
Each form of porphyria results from mutations in specific genes (such as ALAD, ALAS2, CPOX, FECH, HMBS, PPOX, UROD, or UROS) that provide instructions for making enzymes needed to produce heme. Mutations reduce enzyme activity, limiting heme production and causing damaging compounds called porphyrins and porphyrin precursors to build up in the body.
Inheritance
Inheritance patterns vary by type:
- Autosomal Dominant: One mutated copy of the gene is sufficient to increase the risk of symptoms. This includes acute intermittent porphyria, most cases of erythropoietic protoporphyria, hereditary coproporphyria, and variegate porphyria.
- Autosomal Recessive: Both copies of the gene must be mutated. This includes ALAD deficiency porphyria, congenital erythropoietic porphyria, and some cases of erythropoietic protoporphyria.
- X-linked: When caused by ALAS2 mutations, the condition follows an X-linked pattern of inheritance.