Summary about Disease
Coproporphyria (HCP) is a rare, inherited metabolic disorder affecting the heme biosynthetic pathway. This pathway is responsible for producing heme, a component of hemoglobin that carries oxygen in the blood, and other essential proteins. In HCP, a deficiency in the enzyme coproporphyrinogen oxidase leads to the accumulation of porphyrin precursors, specifically coproporphyrinogen, primarily in the liver. This accumulation can cause a range of symptoms, particularly affecting the nervous system, skin, and abdomen. The disease is characterized by acute attacks that can be life-threatening.
Symptoms
Symptoms of HCP can vary widely in severity and presentation. Some individuals with the genetic mutation may remain asymptomatic, while others experience severe attacks. Common symptoms include:
Abdominal pain: Often severe, crampy, and poorly localized.
Nausea and vomiting: Can lead to dehydration and electrolyte imbalances.
Constipation: A common gastrointestinal symptom.
Neurological problems: Muscle weakness, paralysis (especially in the arms and legs), seizures, mental status changes (confusion, hallucinations), anxiety, and depression.
Skin sensitivity to sunlight (photosensitivity): Less common in HCP compared to other porphyrias but can occur, leading to blistering and scarring.
Red or brown urine: Due to the excretion of porphyrin precursors.
Increased heart rate (tachycardia) and high blood pressure (hypertension).
Causes
HCP is caused by a mutation in the CPOX gene, which provides instructions for making the coproporphyrinogen oxidase enzyme. This enzyme is crucial for the sixth step in the heme biosynthesis pathway. A mutation in the *CPOX* gene reduces the amount of functional coproporphyrinogen oxidase, leading to a buildup of coproporphyrinogen in the liver and other tissues. The disease is inherited in an autosomal dominant pattern. This means that only one copy of the mutated gene is needed to cause the disorder. In most cases, an affected person inherits the mutated gene from one affected parent. However, new mutations can also occur.
Medicine Used
The management of HCP involves treating acute attacks and preventing future episodes.
Hemin: This is a key medication used during acute attacks. Hemin (Panhematin) helps to suppress the production of porphyrin precursors in the liver.
Glucose: Intravenous glucose may be administered to help reduce porphyrin production.
Pain management: Analgesics (pain relievers) are used to alleviate abdominal and other pain. Opioids may be necessary for severe pain, but should be used with caution due to potential risks.
Beta-blockers: May be used to control tachycardia and hypertension.
Anti-emetics: Used to treat nausea and vomiting.
Lorazepam or diazepam: To help with anxiety or seizures.
Givosiran (Givezla): An siRNA therapy approved for acute hepatic porphyrias, including HCP, to reduce the production of ALAS1 in the liver, thereby reducing the accumulation of porphyrin precursors. Medications known to trigger attacks should be avoided. A healthcare provider specializing in porphyria should be consulted for a comprehensive list of safe and unsafe medications.
Is Communicable
No, HCP is not communicable. It is a genetic disorder caused by a gene mutation and cannot be spread from person to person through contact or any other means.
Precautions
Individuals with HCP should take the following precautions:
Avoid known triggers: Certain medications (barbiturates, sulfonamide antibiotics, etc.), alcohol, smoking, stress, infections, and hormonal changes (in women) can trigger attacks.
Maintain a healthy diet: Avoid prolonged fasting or calorie restriction. A balanced diet with adequate carbohydrates is recommended.
Avoid exposure to toxins: Some environmental toxins and chemicals can trigger attacks.
Manage stress: Use relaxation techniques, meditation, or counseling to manage stress.
Wear protective clothing and sunscreen: If photosensitivity is present, protect skin from sunlight.
Inform healthcare providers: Always inform doctors and dentists about the diagnosis of HCP before any medical procedures or prescriptions.
Genetic counseling: Consider genetic counseling if planning to have children.
How long does an outbreak last?
The duration of an acute porphyria attack can vary considerably from person to person. An attack can last for several days to several weeks. Early diagnosis and prompt treatment can shorten the duration and severity of the attack. Untreated or severe attacks can lead to prolonged symptoms and potentially life-threatening complications.
How is it diagnosed?
Diagnosis of HCP involves a combination of clinical evaluation and laboratory testing:
Clinical evaluation: A doctor will assess the patient's symptoms, medical history, and family history.
Urine porphyrin analysis: Elevated levels of coproporphyrin in the urine are a key diagnostic marker. A 24-hour urine collection is often used.
Fecal porphyrin analysis: Elevated levels of coproporphyrin in the feces can also be detected.
Plasma porphyrin analysis: Can help to identify the specific type of porphyria.
Enzyme assay: Measurement of coproporphyrinogen oxidase enzyme activity in red blood cells or fibroblasts.
Genetic testing: Identification of a mutation in the CPOX gene confirms the diagnosis. This is usually performed through DNA sequencing.
Timeline of Symptoms
The onset and progression of symptoms in HCP can vary.
Asymptomatic periods: Many individuals with the genetic mutation remain asymptomatic throughout their lives.
Trigger and onset: Acute attacks are often triggered by certain factors (medications, alcohol, stress, etc.). The initial symptoms may include abdominal pain, nausea, and vomiting.
Progression: If untreated, the symptoms can progress to include neurological problems (muscle weakness, paralysis, seizures, mental status changes) and other complications.
Resolution: With treatment (hemin, glucose, supportive care), symptoms gradually improve over days to weeks.
Recurrence: Individuals may experience recurrent attacks, especially if triggering factors are not avoided.
Important Considerations
Differential diagnosis: HCP can be difficult to diagnose because its symptoms overlap with other conditions (e.g., acute abdomen, neurological disorders). It is important to consider porphyria in the differential diagnosis of unexplained abdominal pain and neurological symptoms.
Medication safety: Patients with HCP must avoid certain medications that can trigger attacks. A healthcare provider specializing in porphyria should be consulted for guidance on safe medications.
Long-term management: Even during remission, individuals with HCP need to follow precautions to prevent future attacks.
Family screening: Family members of affected individuals should be offered genetic testing to determine if they carry the CPOX gene mutation.
Specialized care: Management of HCP is best handled by a team of healthcare professionals with experience in porphyria, including hematologists, neurologists, and gastroenterologists.