Acute Hepatic Porphyria

Acute Hepatic Porphyria: Symptoms, Causes, Types, Diagnosis, and Treatments

Acute Hepatic Porphyria (AHP) is a rare but potentially life-threatening group of genetic disorders that affect the liver’s ability to produce heme, a crucial component of hemoglobin. While porphyria is not widely known, those who suffer from AHP may experience severe and unexplained symptoms, often leading to misdiagnosis and delayed treatment.

In this article, we will explore everything you need to know about Acute Hepatic Porphyria—its symptoms, causes, types, diagnostic methods, and available treatment options.

Introduction to Acute Hepatic Porphyria

Acute Hepatic Porphyria (AHP) encompasses a group of rare inherited metabolic conditions characterized by sudden attacks of severe symptoms, primarily involving the nervous system and gastrointestinal tract. The attacks are often episodic, with symptom-free intervals in between.

These conditions stem from abnormalities in the heme biosynthesis pathway, particularly in the liver, where toxic byproducts accumulate during an attack. These toxic substances affect the nervous system, leading to painful and sometimes dangerous complications.

Understanding Heme and the Liver

To understand AHP, it’s important to grasp the basics of heme synthesis. Heme is a molecule that plays a critical role in transporting oxygen in the blood and breaking down toxins in the liver.

The process of heme synthesis involves eight enzymatic steps. In AHP, one of these enzymes is deficient or malfunctioning, causing the accumulation of precursor compounds like aminolevulinic acid (ALA) and porphobilinogen (PBG)—both of which are neurotoxic.

Since most of these enzymes are active in the liver, any defect impacts hepatic (liver-based) production, giving rise to the term “hepatic porphyria.”

What Causes Acute Hepatic Porphyria?

AHP is caused by genetic mutations that affect enzymes involved in the heme production pathway. These are typically autosomal dominant conditions, meaning a person only needs one copy of the defective gene from either parent to be at risk.

However, having the gene does not always result in symptoms. In fact, up to 90% of individuals with the mutation never experience an attack. Symptoms usually occur when environmental or lifestyle factors trigger the condition.

Common Triggers Include:

• Hormonal changes, especially in women (e.g., menstrual cycle, oral contraceptives)
• Certain medications (e.g., barbiturates, sulfonamides)
• Alcohol consumption
• Smoking
• Fasting or crash dieting
• Infections
• Stress and surgery

Understanding and avoiding these triggers is crucial for people at risk.

Types of Acute Hepatic Porphyria

There are four recognized types of Acute Hepatic Porphyria, all involving liver enzyme deficiencies and acute attacks:

Acute Intermittent Porphyria (AIP)

• Most common type
• Caused by a deficiency in the enzyme porphobilinogen deaminase
• Common in women of childbearing age
• Neurovisceral symptoms without skin involvement

Variegate Porphyria (VP)

• Caused by a deficiency of protoporphyrinogen oxidase
• Combines neurovisceral symptoms with photosensitive skin lesions
• Common in South African populations

Hereditary Coproporphyria (HCP)

• Deficiency of coproporphyrinogen oxidase
• Neurological and abdominal symptoms, plus skin sensitivity

ALA-Dehydratase Deficiency Porphyria (ALADP)

• Extremely rare
• Caused by a deficiency of ALA dehydratase
• Often presents in childhood with severe neurotoxicity

Common Symptoms of AHP

Symptoms of AHP can be episodic, and they often appear suddenly and intensely. An attack can last from several days to weeks if not treated promptly.

Neurological Symptoms

• Severe abdominal pain (most common presenting symptom)
• Peripheral neuropathy (tingling, numbness, weakness)
• Muscle pain and cramping
• Seizures
• Mental changes (confusion, hallucinations, anxiety, paranoia)
• Paralysis in severe cases

Gastrointestinal Symptoms

• Nausea and vomiting
• Constipation
• Abdominal distention

Cardiovascular and Urinary Symptoms

• Tachycardia (rapid heartbeat)
• Hypertension
• Dark or reddish urine (due to accumulated porphyrins)

Long-Term Complications

• Chronic pain
• Kidney damage
• Hypertension
• Liver damage or hepatocellular carcinoma in rare cases

Early detection and management are critical to prevent irreversible damage.

Diagnosing Acute Hepatic Porphyria

Diagnosing AHP can be challenging due to the vague and overlapping nature of symptoms, which can mimic many other disorders such as appendicitis, multiple sclerosis, or psychiatric illness.

Urine Tests

• Porphobilinogen (PBG) and aminolevulinic acid (ALA) levels during an attack
• Dark-colored urine may provide a visual clue

Blood Tests

• Plasma porphyrin levels
• Liver function tests

Stool Tests

• To measure porphyrin concentrations, particularly in VP and HCP

Genetic Testing

• Confirms the specific enzyme deficiency
• Helps with family screening and genetic counseling

Imaging

• Occasionally used to rule out other causes of abdominal pain (CT scan, ultrasound)

Accurate diagnosis typically requires a high index of suspicion and detailed patient history, especially concerning symptom triggers.

Treatment Options for AHP

There is no definitive cure for AHP, but various treatments can help manage symptoms, prevent attacks, and improve quality of life.

Hospitalization During Acute Attacks

• Intravenous glucose (carbohydrate loading) to inhibit heme synthesis
• Pain management with opioids
• Anti-nausea medications
• Electrolyte and fluid balance monitoring

Hemin Infusion (Panhematin® or Normosang®)

• Synthetic heme analog that inhibits ALA synthase
• Reduces production of toxic porphyrin precursors
• Administered intravenously, often during or shortly before attacks

Givosiran (Givlaari®)

• FDA-approved RNA interference therapy
• Reduces ALA production by silencing ALAS1 mRNA
• Monthly subcutaneous injection
• Effective for patients with frequent or recurrent attacks

Symptomatic Treatment

• Anticonvulsants for seizures (avoid enzyme-inducing drugs)
• Beta-blockers for hypertension
• Antidepressants or antipsychotics for mental symptoms (with caution)

Liver Transplantation

• Considered in severe, unmanageable cases
• Can be curative but carries risks of surgical complications and immunosuppression

Living with AHP: Lifestyle and Management

Management doesn’t end with medications—patients must learn how to navigate life while minimizing attack risks.

Avoiding Triggers

• Maintain regular meals to avoid fasting
• Avoid unsafe drugs (check porphyria-safe drug lists)
• Limit alcohol and smoking
• Manage stress with relaxation techniques

Women’s Health

• Hormonal fluctuations can trigger attacks
• Use of oral contraceptives must be carefully evaluated
• Pregnancy may improve or worsen symptoms

Support Systems

• Psychological counseling
• Porphyria patient groups and networks
• Regular follow-ups with a multidisciplinary team (neurologist, hepatologist, geneticist)

Genetic Counseling

• Family members should be tested
• Prenatal testing may be available in high-risk families

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Outlook and Prognosis

With timely diagnosis and proper management, many patients with AHP can live relatively normal lives. However, misdiagnosis or delayed treatment can lead to irreversible nerve damage, chronic pain, and organ dysfunction.

Recent advances like givosiran have significantly improved the prognosis for patients with recurrent AHP. Early genetic screening and better awareness can further reduce the burden of this rare but serious condition.

Conclusion

Acute Hepatic Porphyria is a complex, often misunderstood condition that can have serious health consequences if not properly diagnosed and treated. By understanding the symptoms, triggers, and available treatments, patients and healthcare providers can work together to manage the condition effectively.

Frequently Asked Questions (FAQs) About Acute Hepatic Porphyria

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