Porphyria

Overview

Porphyria encompasses a collection of rare disorders characterized by an accumulation of natural chemicals called porphyrins, which are essential for producing heme, a component of the hemoglobin protein in red blood cells. Hemoglobin is crucial for transporting oxygen to the body’s organs and tissues. The synthesis of heme requires eight specific enzymes, and a deficiency in any of these enzymes leads to an excessive buildup of porphyrins, causing significant health issues, particularly affecting the nervous system and skin.

There are two primary categories of porphyria: acute and cutaneous. Acute porphyrias manifest rapidly with predominantly neurological symptoms, while cutaneous porphyrias primarily cause skin problems. Some forms of porphyria impact both the nervous system and the skin. Symptoms vary widely depending on the type and severity of the disorder, but they generally include neurological and dermatological manifestations.

Although there is no cure for porphyria, it can often be managed with medication and lifestyle adjustments. Treatment strategies are tailored to the specific type of porphyria, focusing on symptom management. While most types of porphyria are hereditary, passed down from parents to children, one common type, porphyria cutanea tarda (PCT), may not always be inherited.

Symptoms

Systemic mastocytosis and porphyria are two different conditions that present with varying symptoms depending on the affected body parts and the specific type of each condition.

Systemic mastocytosis

Systemic mastocytosis involves an abnormal accumulation of mast cells in various body tissues, including the skin, liver, spleen, bone marrow, and intestines, and occasionally in the brain, heart, or lungs. Symptoms can vary widely:

• Skin: Flushing, itching, hives
• Gastrointestinal: Abdominal pain, diarrhea, nausea, vomiting
• Hematologic: Anemia, bleeding disorders
• Musculoskeletal: Bone and muscle pain
• Organ Enlargement: Liver, spleen, lymph nodes
• Neurological/psychological: Depression, mood changes, concentration problems

Triggers for mast cell activation in systemic mastocytosis commonly include alcohol, skin irritation, spicy foods, exercise, insect stings, and certain medications.

Consult your physician if you experience flushing, hives, or if any of the above symptoms concern you.

Porphyria

Porphyria refers to a group of disorders that can affect the skin or nervous system, with symptoms ranging from mild to severe and potentially life-threatening.
Cutaneous Porphyria: Primarily affects the skin, leading to:

• Oversensitivity to sunlight
• Itching, swelling on sun-exposed skin
• Skin abrasions, blisters, erosions
• Scarring and fragile skin in sun-exposed areas

Acute porphyrias: Affects the nervous system with sudden, short-term symptoms:

• Severe pain in the abdomen, chest, limbs, or back
• Nausea, vomiting, constipation, urinary retention
• Mental changes like confusion and hallucinations
• Seizures, muscle weakness

Symptoms vary by the type of porphyria, and some individuals may be asymptomatic. Urgent medical attention is often required during acute episodes.

Causes

In each type of porphyria, there is a shortage of a specific enzyme crucial for producing heme, an important iron-containing pigment vital for the body’s organs. Heme is a key component of hemoglobin in blood, which carries oxygen and gives red blood cells their color. It is also essential for liver proteins, aiding in liver function.

The production involves eight enzymes in the bone marrow and liver converting porphyrins into heme. Any deficiency or alteration in these enzymes leads to a porphyrin buildup. These compounds accumulate in the liver, skin, and other tissues, potentially leading to symptoms of porphyria.
Each type of porphyria has varying causes, such as:

• Genetic mutations: Porphyria can occur when an individual inherits a modified gene from one parent or from both parents. However, many carriers may never exhibit any signs of the condition. Thus, simply inheriting these altered genes does not necessarily lead to the manifestation of symptoms.
• Acquired forms: Porphyrins can accumulate in response to specific triggers, which may result in symptoms. This is particularly common in porphyria cutanea tarda (PCT). Triggers can include things like:
  • Hemochromatosis, a genetic disorder that causes excessive iron in the body
  • Hormonal changes during menstruation
  • Cigarette consumption
  • Excessive alcohol consumption
  • Viral illnesses, like hepatitis C or HIV

Risk factors

In most cases, genetic mutations inherited from parents cause porphyria in their offspring. If a parent suffers from porphyria, a child’s risk of developing the condition also increases.

Environmental risk factors can exacerbate porphyria symptoms. Porphyria Cutanea tarda (PCT) is distinct from other forms of porphyrias in that it arises from the reactivation of an inactive acquired disease. The body needs more time to produce hemes when it is exposed to the trigger.

Exposure to the following triggers increases the risk for PCT:

• Alcohol consumption
• Tobacco consumption
• Sunlight exposure
• Hormonal fluctuations
• Some medications, such as barbiturates, sedatives, and birth control tablets
• Stress resulting from emotional or physical conditions including infections, diseases, or surgery
• Illegal or recreational drugs
• Fasting and dieting
• Hemochromatosis
• Chronic hepatitis C
• HIV