Summary about Disease
Variegate porphyria (VP) is a rare genetic metabolic disorder affecting the production of heme, a component of hemoglobin. It is characterized by acute attacks involving the nervous system, skin problems (photosensitivity), or both. Symptoms vary widely and not everyone with the genetic mutation will experience symptoms. The disease results from a deficiency in the enzyme protoporphyrinogen oxidase (PPOX) within the heme biosynthetic pathway.
Symptoms
Symptoms of VP can include:
Severe abdominal pain
Nausea and vomiting
Constipation
Muscle weakness, pain, and cramps
Seizures
Mental status changes (e.g., anxiety, confusion, hallucinations)
Red or brown urine (during attacks)
Photosensitivity (blisters, scarring, and increased skin fragility upon sun exposure)
Pain in the arms or legs
High blood pressure and heart rate
Causes
VP is caused by a mutation in the PPOX gene, which provides instructions for making the protoporphyrinogen oxidase enzyme. This enzyme is crucial for heme production. A deficiency of this enzyme leads to a buildup of porphyrin precursors in the body, which can cause the symptoms of VP. The condition is inherited in an autosomal dominant pattern, meaning that only one copy of the mutated gene is needed to cause the disorder.
Medicine Used
During acute attacks, medications used may include:
Hemin (Panhematin or Normosang): This medication is a form of heme that helps to reduce the production of porphyrin precursors.
Glucose: Intravenous glucose can help reduce porphyrin production.
Pain medication: Opioids are often required to manage severe pain.
Anti-emetics: To reduce nausea and vomiting.
Beta-blockers: To manage high blood pressure and rapid heart rate.
Lorazepam or Diazepam: To treat anxiety, agitation, and/or seizures.
Givosiran (Givezla): A siRNA medication that reduces the production of ALAS1 in the liver. For chronic photosensitivity:
Beta-Carotene may help reduce photosensitivity.
Is Communicable
No, variegate porphyria is not communicable. It is a genetic disorder and cannot be transmitted from person to person through infection or other means.
Precautions
Individuals with VP should take the following precautions:
Avoid triggers: Identify and avoid factors that can trigger attacks, such as certain drugs (barbiturates, sulfonamide antibiotics, tranquilizers), alcohol, smoking, dieting/fasting, stress, and hormonal changes (menstrual cycle).
Sun protection: Protect skin from sun exposure with protective clothing, hats, and sunscreen with high SPF.
Diet: Maintain a healthy diet and avoid prolonged fasting or crash diets.
Medication awareness: Inform all healthcare providers about the VP diagnosis, and carry a list of safe and unsafe medications.
Genetic Counseling: If planning a family, genetic counseling is recommended to assess the risk of passing the gene on to offspring.
Avoid Alcohol and Smoking: Both can trigger attacks.
How long does an outbreak last?
The duration of an acute VP attack varies considerably. Some attacks may resolve within a few days, while others can persist for weeks or even months if left untreated or if complications arise. The length of an attack is influenced by the severity of the enzyme deficiency, the presence of triggering factors, the timeliness of diagnosis and treatment, and individual response to therapy. Chronic photosensitivity may persist indefinitely.
How is it diagnosed?
Diagnosis of VP typically involves:
Clinical evaluation: Assessment of symptoms and medical history.
Biochemical testing:
Urine porphyrins and porphyrin precursors (ALA and PBG): Elevated levels are often found during acute attacks.
Fecal porphyrins: Increased levels of specific porphyrins can help differentiate VP from other porphyrias.
Plasma porphyrins: Evaluation of porphyrin profiles in blood.
Genetic testing: PPOX gene sequencing to identify mutations. This is the most definitive diagnostic test.
Enzyme testing: Measurement of protoporphyrinogen oxidase (PPOX) activity in blood cells.
Wood's lamp examination: Examination of urine under Wood's lamp may show a characteristic fluorescence pattern.
Timeline of Symptoms
The onset and progression of VP symptoms vary.
Childhood/Adolescence: Onset is rare before puberty.
Early Adulthood: The most common time for the first attack.
Attacks: Sudden onset of severe abdominal pain, neurological symptoms, and/or photosensitivity.
Chronic Photosensitivity: May develop gradually over time with repeated sun exposure.
Intermittent: Individuals may be asymptomatic between attacks, or they may experience chronic symptoms such as fatigue or mild pain.
Progression: Repeated attacks can lead to chronic neurological or kidney damage.
Important Considerations
Early diagnosis is crucial to prevent complications and improve outcomes.
Awareness of triggers and proactive avoidance is essential for managing the condition.
Treatment focuses on managing acute attacks and preventing future episodes.
Genetic counseling is important for families with a history of VP.
Long-term monitoring is necessary to detect and manage potential complications, such as liver or kidney damage.
Support groups and patient advocacy organizations can provide valuable resources and support.
Individuals with VP should wear a medical alert bracelet to ensure appropriate treatment in emergency situations.
Prophylactic treatment with Givosiran may be considered to prevent attacks.