Porphyria - Types, Symptoms, Causes, Diagnosis, Treatment and Prevention

What Is Porphyria?

Porphyria is named after a Greek word called Porphura, meaning purple. Porphyria is a group of blood disorders, which is rare and inherited, in which the body is not able to make heme properly. Heme is a component of hemoglobin (a protein in red blood cells that helps carry oxygen to the organs and tissues and transports carbon dioxide from organs and tissues back to the lungs) that gives the red color to the red blood cells (RBCs) and helps them carry oxygen. Heme is made of porphyrin, which is bound to iron and occurs naturally in the body. This compound is also found in myoglobin, a protein in muscles.

Porphyria patients lack the enzymes needed to complete the production of heme, which results in the accumulation of porphyrin in tissues and blood, causing symptoms. The symptoms vary among people depending upon the deficiency of the specific enzyme. The most common symptoms are stomach pain, rash or blister due to light sensitivity, and muscle problems.

Porphyrias are mostly inherited, but rarely they are acquired. All types of porphyrias are inherited as autosomal dominant disorders except congenital erythropoietic porphyria (CEP), which is autosomal recessive. Some porphyrias result in severe and acute symptoms, while some are chronic and cause less severe symptoms.

What Are the Types of Porphyria?

The two main types of porphyria are -

Acute - It primarily affects the nervous system, as it causes damage to nerve cells due to the build-up of chemicals used to make heme. Only one in five people experience symptoms, and the symptoms are usually not seen before puberty or after menopause.

Cutaneous - This type affects the skin. Here, the build-up of porphyrin causes rashes and blisters on the skin due to exposure to sunlight (photosensitivity). It is less severe than acute porphyria and is more common than the acute type. It is further classified into the following types -

Hepatic - These types of porphyrias are associated with liver problems. The subtypes include:

• Acute Intermittent Porphyria (AIP) - It is caused by the deficiency of the enzyme hydroxymethylbilane synthase (HMBS). The symptoms do not appear unless triggered by hormonal changes, specific drug usage, alcohol consumption, dietary changes, and infections.

• Hereditary Coproporphyria (HCP) - This is caused by a deficiency of the enzyme coproporphyrinogen oxidase (CPOX). It is seen in both men and women equally, and the symptoms occur only by specific triggers like behavioral, environmental, or hormonal changes.

• Variegate Porphyria (VP) - This can be characterized by chronic blistering cutaneous manifestations and acute neurovisceral attacks (relating to both the nervous and cerebrospinal systems) manifestations that may become chronic.

• Delta-aminolevulinate-dehydratase deficiency Porphyria (ALAD) - It is a rare and severe type of porphyria caused by the deficiency of the enzyme delta-aminolevulinic acid (ALA). There have been reports of only about 10 cases worldwide, and all have been in males.

• Porphyria Cutanea Tarda (PCT) - A rare type characterized by painful, blistering skin lesions that develop on sun-exposed skin (photosensitivity).

Erythropoietic - These types are caused due to problems in RBCs. The subtypes are:

• X-linked dominant protoporphyria (XLDPP).

• Congenital erythropoietic porphyria (CEP).

• Harderoporphyria.

• Erythropoietic protoporphyria (EPP).

The most common type of porphyria is porphyria cutanea tarda (PCT).

What Are the Symptoms of Porphyria?

Depending on the severity, type, and individual, the symptoms of porphyria can vary widely. However, some of the common symptoms include:

Acute porphyrias -

• Severe stomach pain.

• Pain in the chest, legs, and back.

• Constipation or diarrhea.

• Nausea.

• Vomiting.

• Muscle pain.

• Tingling sensation in the muscles.

• Muscle weakness, numbness, or paralysis.

• Red or brown discoloration of urine.

• Anxiety.

• Confusion.

• Hallucinations.

• Paranoia.

• Breathing difficulties.

• Urination problems.

• Palpitations.

• Hypertension.

• Seizures.

Cutaneous Porphyrias -

• Burning sensation in the skin on exposure to the sun or artificial light.

• Spontaneous skin redness and swelling can be painful.

• Blisters on hands, arms, and face

• The skin becomes thin and fragile.

• Change in skin color.

• Excessive growth of hair in affected areas.

• Red or brown discoloration of urine.

Hepatic Porphyria:

• Pain in arms and legs.

• Neuropathy.

• High blood pressure.

• Fast heartbeat.

• Electrolyte imbalance.

Erythropoietic Porphyria -

• Photosensitivity.

• Anemia.

• Sun exposure results in erratic behaviors.

• Change in skin color or pigmentation.

What Causes Porphyria?

Most types of porphyria are inherited (hereditary). So, according to their genetic nature, they can be -

• Autosomal Dominant - When the defective gene is inherited from one of the parents.

• Autosomal Recessive - When an individual inherits defective genes from both parents.

Some people have the gene or genes but do not show any symptoms.

There are some types of porphyrias that are acquired and not inherited. PCT (porphyria cutanea tarda) is an example of the acquired form, but the enzyme deficiency may be inherited.

What Are the Risk Factors for Porphyria?

Some factors that can trigger symptoms include -

• Too much iron in the body.

• Liver disease.

• Hormonal medication.

• Smoking.

• Alcohol abuse.

• Sunlight.

• Infection.

• Drug abuse.

• Too much stress.

• Dieting and fasting.

What Are the Complications of Porphyria?

Some of the complications of porphyria are:

• Liver failure.

• Kidney failure.

• Hypertension.

• Permanent skin scarring.

• Muscle weakness.

• Paralysis.

• Respiratory failure.

• Gallstones.

How Is Porphyria Diagnosed?

As the signs and symptoms of porphyria are similar to some common diseases, tests are done to rule out all other possible conditions. For example, the doctor might suggest taking tests like computed tomography (CT) scans, chest X-rays, and echocardiogram (EKG or ECG) to rule out physical problems. In some cases, blood and urine tests might also be needed.

How Is Porphyria Treated?

There is no specific treatment for porphyria. Treatment is done by avoiding triggers and treating symptoms.

Acute Porphyrias -

• Hemin Injections - It is a heme administered by injections that limit the production of porphyrins.

• Intravenous or Oral Glucose - Helps to maintain the required intake of carbohydrates.

• Hospitalization - To treat severe symptoms like severe pain, dehydration, and breathing difficulties.

Cutaneous Porphyrias -

• Phlebotomy - To reduce the iron content, blood is drawn periodically, reducing the concentration of porphyrins.

• Antimalarial Drug - Hydroxychloroquine or Chloroquine is used to absorb excess porphyrins.

• Vitamin D Supplements - For vitamin D deficiency, supplements can be given as patients tend to avoid sunlight.

For Hepatic Disease -

• Beta-blockers for hypertension.

• A diet rich in carbohydrates.

• Opioids for pain relief.

• Hematin to shorten the length of attacks.

For Erythropoietic Disease -

• Transfusion of blood.

• Iron supplements for anemia.

• Bone marrow transplantation.

How to Prevent Porphyria?

There is no sure way to prevent this disease, but stopping some triggers can help prevent porphyria, such as -

• Avoid using medications that trigger acute attacks.

• Do not consume alcohol or recreational drugs.

• Do not fast and diet.

• Avoid smoking.

• Do not take hormonal drugs containing estrogen.

Conclusion:

Most people with porphyria usually recover from the symptoms; however, a genetic mutation causes this condition, leading to the appearance of symptoms throughout life. Early diagnosis of this disease can help lead a normal life and easy management of this disease.