Do you have a strange illness that you can't understand? It could be Acute Hepatic Porphyria!

Do you feel like you have an unimaginable stomach ache, sometimes with a heavy heart, and numbness in your limbs? Perhaps even doctors are at a loss to figure out what it is. One of these strange, seemingly unrelated symptoms that we are going to talk about today is Acute Hepatic Porphyria (AHP). Don't worry, this is a bit complicated, but let's understand it simply.

What exactly is acute hepatic porphyria (AHP)?

Simply put, AHP is a very rare genetic disease . It starts in your liver . But it also affects your nervous system , causing symptoms throughout your body. Think about it, there is something called heme, which is part of the hemoglobin in our blood. Our body needs various enzymes to make this heme. A person with AHP has a deficiency, or lack, of some of the enzymes needed to make this heme.

What happens when this happens? Some of the chemicals that should have been used to make heme are left over. We call these leftovers porphyrin precursors . When these build up, they are toxic to the body. In AHP, these toxins first build up in the liver. Then, when they get into the blood and interact with the nerves, the symptoms start to appear. Do you understand?

Are there different types of AHP?

Yes, there are four main types of AHP. These four types are divided into the types of enzymes I mentioned earlier, depending on which enzyme is deficient. Each type is named after the part called "hepatic" because it starts in the liver, and the part called "acute" because the symptoms appear suddenly. In order from the most common type to the least common, here are the types:

1. Acute Intermittent Porphyria (AIP): This is the most common. A mutation in the HMBS gene causes a deficiency in the enzyme hydroxymethylbilane synthase (HMBS) (also known as porphobilinogen deaminase (PBGD)). This can be a newly occurring genetic mutation, or it can be inherited as an autosomal dominant trait (i.e., the disease can occur even if only one parent inherits the gene).

2. Variegate Porphyria (VP): A mutation in the PPOX gene causes a deficiency in the enzyme protoporphyrinogen oxidase (PPO or PPOX). This can also be inherited as autosomal dominant or autosomal recessive.

3. Hereditary Coproporphyria (HCP): A mutation in the gene `CPOX` results in a deficiency of the enzyme `coproporphyrinogen oxidase (CPOX).` This can also be inherited as autosomal dominant or autosomal recessive.

4. ALAD-Deficiency Porphyria (ADP): A mutation in the `ALAD` gene causes a deficiency of the enzyme `delta-aminolevulinic acid dehydratase (ALAD). This is inherited in an `autosomal recessive` manner (i.e., the disease can only occur if both parents inherit the gene).

How does AHP affect me?

This is surprising, because AHP does not affect everyone the same. Some people have the gene mutation for it but do not develop any symptoms . Others may have "attacks" of symptoms only once or twice in their lifetime. But some people have these attacks frequently, and others have them chronically , meaning they continue to have symptoms that affect their daily lives. Sometimes an attack can be so severe that you may need to be rushed to the hospital emergency room. You may experience severe nerve pain, skin changes, and symptoms related to the nervous system.

Who is most likely to get this?

AHP can affect people of any race or color. It can be inherited from one or both parents who have the gene mutation. Surprisingly, many people do not develop symptoms . For symptoms to develop, the gene mutation alone is not enough. Several other `triggers` must also be present.

What are these triggering factors?

• Hormonal changes (especially during puberty, pregnancy, and the menstrual cycle)
• Some medications
• Alcohol use
• Smoking
• Severe stress
• Strict dietary control (especially calorie restriction)

It is also noteworthy that 80% of those who develop symptoms are women of childbearing age .

How common is AHP?

It is difficult to say for sure, because this disease is often not properly diagnosed. Worldwide, it is estimated that about 5 out of 100,000 people may have it. Of the previously mentioned types, `Acute Intermittent Porphyria (AIP)` is the type that is seen in only 80% of the reported cases. `ALAD-Deficiency Porphyria (ADP)` is the least common type, with only 9 cases reported worldwide. Imagine, only one out of every 10 people with the gene mutation related to AHP will develop symptoms.

What are the symptoms of AHP?

The symptoms of AHP are very strange. They can be difficult for patients and doctors to understand, because the symptoms can appear suddenly, be severe, and seem unrelated to each other.

Here are some of these features:

Nerve pain

This pain can occur in various places in the body:

• Severe abdominal pain – This is the first symptom that occurs to most people.
• Chest pain
• Back pain
• Pain in the hands and feet

Digestive system problems

Because the nerves are affected, problems with the digestive system can also occur:

• Nausea and vomiting
• Indigestion
• Constipation
• Diarrhea

Central nervous system symptoms

These are directly related to the brain and mind:

• Anxiety
• Insomnia
• Depression
• Delirium
• Hallucinations – seeing or hearing things that are not really there
• Status epilepticus/seizure (`Seizure`)

Peripheral nervous system symptoms

These are connected to nerves in other parts of the body:

• Muscle weakness
• Numbness and tingling in the limbs
• Fatigue
• Sensory loss
• Muscle paralysis
• Respiratory paralysis – This is very dangerous and can cause difficulty breathing.

Autonomic nervous system symptoms

These are things that happen spontaneously, things that we have no control over:

• Heart palpitations
• High blood pressure

Skin symptoms (especially in `Variegate Porphyria` and `Hereditary Coproporphyria`)

People with these two types may experience skin problems when exposed to the sun :

• Sensitivity to sunlight
• Blistering rash
• Skin discoloration (Pigmentation)
• Scarring

The most important thing is that when you have porphyria, your urine may change color . When those porphyrin precursors I mentioned accumulate in your body and are excreted in your urine, your urine can turn a reddish-purple color . The word "porphyria" comes from the Greek word "porphura," which means "purple." The porphyrins in our red blood cells are what give blood its red color.

What is an AHP attack?

For many people with AHP symptoms, these come in the form of occasional "attacks." Some people experience them more frequently, some less frequently. Some people experience them more severely, while others don't. Usually, these attacks last for a few days, and then gradually increase and decrease. If you have severe, frightening symptoms, you should go to the hospital. As I said, things like respiratory paralysis, which makes it difficult to breathe, are conditions that require emergency medical attention.

The most common symptom of an AHP attack is unexplained, severe stomach pain . More than 90% of people with AHP go to a doctor because of this stomach pain. However, because there are many causes of stomach pain, and because neither an X-ray nor a CT scan can find the cause of this pain (because it is nerve pain), it is very difficult to diagnose. Because this stomach pain is accompanied by things like nausea, vomiting, and constipation, doctors may think that it is a digestive disease. If you also have mental and sensory problems, they may think that it is a neurological disease. When these seemingly unrelated symptoms come together, it is necessary to see a doctor who knows about it.

What chronic symptoms can AHP cause?

People with milder disease (less enzyme deficiency) rarely experience chronic symptoms. They may only have one or two attacks in their lifetime. If they identify their triggers, they can avoid them. However, some people have frequent attacks, and some symptoms are so frequent that they can be considered chronic. Such symptoms include:

• Pain
• Tiredness
• Nausea
• Neuropathy ( numbness, pain, or weakness in the limbs)

What are the complications of AHP?

Symptoms related to the central nervous system (such as anxiety, hallucinations, and seizures) usually occur only during an attack. However, symptoms related to the peripheral nervous system (such as muscle weakness and paralysis) can occur frequently, and permanent damage can occur after a severe attack. The accumulation of these porphyrin precursors can also cause long-term damage to certain organs. These may include:

• Chronic hypertension
• Chronic liver disease
• Chronic kidney disease
• Primary liver cancer
• Depression and anxiety

What causes AHP?

The main cause of AHP is genetic mutations . But as I said before, symptoms do not appear immediately after the genetic mutation is present. In most cases, symptoms first appear during puberty, along with hormonal changes. In addition, certain medications, drugs, excessive alcohol consumption, severe calorie restriction, and illnesses that put a lot of stress on the body can also trigger it.

What all of these triggers have in common is that they stimulate the liver's heme production process. However, in the liver of someone with AHP, the byproducts of heme production (such as porphyrin precursors) are not properly metabolized, that is, used up. Therefore, these leftover porphyrin precursors accumulate in the liver. It is only when these accumulate to a certain level that they begin to affect the nervous system and cause symptoms.

How is AHP diagnosed? (Diagnosis)

Getting a proper diagnosis can be a challenge for people with AHP. The symptoms are not unique to the disease and may seem unrelated. However, a doctor who is familiar with AHP may suspect that you have AHP if you have central and peripheral nervous system symptoms along with abdominal pain. The combination of these three symptoms is considered the "classic triad" of AHP.

If a doctor suspects AHP, they may perform several tests to confirm it.

• Urine test: This can be done quickly during an attack. Urine may be normal when you are not having an attack, but during an attack, the urine will show elevated levels of porphyrin precursors (PBG and ALA). This is not a test that is done exclusively for AHP, but it is a basic test that can help doctors point you in the right direction.
• Genetic testing: This is the best and most definitive way to diagnose AHP (the `gold standard`) . Whether you have symptoms or not, it can confirm whether you have a gene mutation that is associated with AHP. It can also tell you which type of AHP you have and how severe the enzyme deficiency is. This involves taking a blood or saliva sample. Your local hospital may also need to send the sample to a specialized lab.

How is AHP treated?

Treatment for AHP focuses on preventing and controlling attacks . You may need to be hospitalized during an attack. You may need different types of medication to reduce your symptoms. During the periods when you are not having attacks, you may need other medications to control the triggers that make your symptoms worse. If you and your doctor work together to identify the triggers that affect you the most, your treatment will be more effective.

Treatment for a severe attack:

• Hemin injection: In the event of a severe attack, a doctor may give you an injection of hemin into a vein. This helps reduce the amount of porphyrin in your blood. Hemin is a substance that is taken from red blood cells and reduces the amount of porphyrin in your body.
• Pain relief: In a severe attack, strong painkillers such as opioids may be needed.
• Phenothiazines: These are used to control severe nausea and vomiting.
• IV fluids and nutrition: Symptoms such as stomach pain, nausea, vomiting, diarrhea, and constipation can cause the body to lose calories and water during an attack. AHP can also cause a loss of things like sodium and magnesium. Therefore, fluids containing carbohydrates and electrolytes can be given intravenously.
• Seizure medications: About 20% of patients may require treatment for epilepsy during an attack.

Long-term treatment options:

• Prophylactic hemin: Giving low doses of hemin once a week to people who have frequent attacks can prevent the accumulation of porphyrins.
• Givosiran (GIVLAARI®): This is a type of gene therapy . It reduces the production of porphyrin precursors. It is now approved as a monthly injection to prevent AHP symptoms in people who have frequent attacks.
• Hormone therapy: If your AHP attacks are caused by your menstrual cycle, your doctor may prescribe medications like GnRH (Gonadotropin-releasing hormone) analogs. These reduce the body's production of the hormones estrogen and progesterone.
• High blood pressure medication: If chronic high blood pressure develops, it will need to be controlled with specific medications.
• Liver transplantation: People who have frequent, life-threatening attacks and who have not responded to other treatments may consider a liver transplant. This can even cure the disease completely.

Can AHP be prevented?

It is not possible to prevent the disease from occurring. However, you can help prevent symptoms from occurring by avoiding triggers . If you have never had an attack, it is best to avoid all possible triggers. If you have had an attack and have identified the triggers that caused it, it may be enough to avoid just those specific triggers.

Here are some of the most commonly seen triggers:

Types of medicines:

• Antihistamines (some medicines for colds and allergies)
• Sedatives
• Oral contraceptives
• Hormone replacement therapy

Material usage:

• Tobacco (`Tobacco`)
• Marijuana
• Alcohol
• Recreational drugs

Stress:

• Infections
• Surgery
• Low calorie intake (especially low carbohydrate intake) (`Calorie deprivation`)
• Psychological stress

What is the future for people with AHP? (Prognosis)

This varies greatly from person to person. Many people never develop symptoms . Of those who do, most people have only one or a few attacks in their lifetime. Although attacks can be life-threatening, most people make a full recovery with prompt medical treatment . About 5% of people with AHP have frequent or chronic symptoms. For these people, preventive medications are often helpful, and a liver transplant may be considered as a last resort.

How do I take care of myself while living with AHP?

• Avoid common triggers. Alcohol, smoking, and drugs should be at the top of your list of things to avoid. You may also want to talk to your doctor about alternatives to some of the medications you take.
• Eat a healthy, balanced diet. Avoid extreme dieting and low-carb diet plans. If you are fasting before a medical test or surgery, talk to your doctor about it.
• Get regular medical checkups. Even if you don't have symptoms, your doctor will regularly check your liver, kidneys, and blood pressure.

Acute hepatic porphyria is a rare disease, so awareness about it among the general public is low. When an attack comes on suddenly with severe symptoms, it is very confusing and scary. Some people spend years trying to figure out what is wrong with them and what they can do. If you suspect you have AHP, a genetic test can confirm it. Once you know, it will be a great help for you to prevent attacks and control them.

The most important things you need to know (Take-Home Message)

Okay, so let me summarize some of the things you need to remember from what we've talked about:

• AHP is a rare genetic disease that starts in the liver and affects the nervous system .
• This is due to a deficiency of enzymes needed in the process of making heme , which causes toxic substances called porphyrin precursors to accumulate in the body.
• Symptoms can be varied, ranging from unrelated, severe stomach pain, nerve pain, mental problems, skin problems, and even changes in the color of your urine.
• Even if the genetic mutation is present, symptoms rarely appear without triggers ( such as hormones, certain medications, alcohol, and stress).
• Urine tests and genetic testing are important for diagnosis.
• The main thing is to control and prevent attacks through treatment. `Hemin` vaccine, painkillers, and some special medications are used. In the most severe cases, a liver transplant is also a solution.
• You can live well with the disease by avoiding triggers, leading a healthy lifestyle, and getting regular medical checkups .

I hope this information is helpful to you. Remember, if you have any of these symptoms, don't be afraid to see a doctor and talk about it.

` Acute hepatic porphyria, AHP, liver, nervous system, genetic diseases, porphyrins, symptoms, treatment