Acute hepatic porphyria (AHP) is a group of four genetic diseases that affect the nervous system. Each type causes attacks of belly pain and other symptoms that range from mild and occasional to severe and frequent.
AHP is rare, and its symptoms look like the symptoms of other more common conditions. These things make it difficult to diagnose. It can sometimes take years to get the right diagnosis.
Undiagnosed AHP increases the risk for serious complications and can even be life-threatening. That's why it's important to see a doctor if you have symptoms and advocate for yourself until you get a diagnosis.
Why Is AHP So Challenging to Diagnose?
One reason why AHP is so hard to diagnose is because it's very rare.
On top of that, AHP symptoms like belly and back pain, nausea and vomiting, tiredness, and anxiety are also symptoms of more common conditions. AHP can look very similar to heart disease, digestive diseases, gynecologic issues, and even mental health conditions like depression and anxiety.
Many of its symptoms don't seem to go together. Doctors who aren't familiar with AHP can easily miss it.
Diagnosing AHP is often a frustrating process. People with this condition wait an average of 15 years after their symptoms start to finally get a diagnosis. Some see several different doctors before they finally get answers to what’s behind their symptoms.
These are some of the conditions that are confused with AHP:
Appendicitis: Inflammation of the appendix.
Symptoms shared with AHP: Belly pain, nausea and vomiting, constipation, diarrhea
Cholecystitis: Inflammation of the gallbladder.
Symptoms shared with AHP: Belly pain, nausea, vomiting
Colitis: Inflammation of the colon, the bottom part of the large intestine.
Symptoms shared with AHP: Belly pain, diarrhea, nausea and vomiting, tiredness
Endometriosis: A gynecologic condition where tissue that's like the lining of the uterus grows in other parts of the belly.
Symptoms shared with AHP: Belly pain, tiredness, constipation, nausea.
Epilepsy: A problem with signaling between nerve cells in the brain that causes seizures.
Symptoms shared with AHP: Seizures, fast heartbeat
Fibromyalgia: A chronic disorder that causes pain in bones and muscles throughout the body.
Symptoms shared with AHP: Pain, fatigue
Guillain-Barre syndrome: A rare autoimmune disease in which the immune system attacks the nerves.
Symptoms shared with AHP: Tingling, weakness, pain, fast heart rate, trouble breathing
Hepatitis: Inflammation of the liver that's sometimes caused by an infection.
Symptoms shared with AHP: Belly pain, muscle pain, tiredness, dark urine
Irritable bowel syndrome (IBS): A chronic condition of the GI tract.
Symptoms shared with AHP: Belly pain, constipation, diarrhea
Psychosis: A mental health disorder where people lose contact with reality.
Symptoms shared with AHP: Hallucinations
Urinary tract infection (UTI): A bacterial infection of the kidneys, bladder, or other parts of the urinary tract.
Symptoms shared with AHP: Belly pain, tiredness, nausea, and vomiting
Risks of Delayed Diagnosis
Getting a prompt diagnosis is important with AHP. If you don't treat it quickly, the attacks could get more severe and happen so often that they disrupt your life. AHP can cause permanent damage to your nervous system as well as complications like these:
- Paralysis of the arms and legs that prevents them from working
- Paralysis of the muscles you need to breathe
- Liver cancer
- Kidney failure
- High blood pressure
AHP can even be life-threatening.
Sometimes doctors misdiagnose people with a disease that has symptoms like AHP. If that happens, they may prescribe a medicine or perform a surgery that you don't need.
Another worry is that if you don't know you have AHP, your doctor might prescribe a medication that makes your attacks worse. Medicines like carbamazepine (Tegretol), which treats seizures, and metoclopramide (Reglan), used to treat nausea, could trigger more AHP attacks.
Advocating for yourself can improve your odds of getting a timely and correct diagnosis. If you have symptoms of AHP and you're not getting answers, ask your doctor to refer you to someone who specializes in diagnosing and treating this condition.
What to Do If You Think You Have AHP
Repeated attacks of severe belly pain that aren't caused by another condition could be AHP. This is especially true for women ages 15 to 50 because they're the group most likely to have AHP symptoms.
See a doctor if you have belly pain plus one or more of these symptoms:
- Nausea and vomiting
- Pain in the back, arms, or legs
- Muscle weakness
- Diarrhea or constipation
- Tiredness
- Fast heartbeat
- Seizures
- Anxiety or depression
- Confusion
- Change in urine color
- Skin blisters
You can start with your primary care doctor. They might refer you to a hematologist – a specialist who diagnoses and treats blood disorders. These doctors may also be part of your diagnostic team:
- Nephrologist: A kidney doctor
- Neurologist: A doctor who diagnoses and treats diseases of the nervous system, which includes the brain, spinal cord, and nerves
- Dermatologist: A doctor who treats skin problems
- Gastroenterologist: A doctor who diagnoses and treats diseases of the GI tract
- Genetic counselor and geneticist: Specialists who use genetic tests to determine your diagnosis and find out if your family members are at risk
Because AHP is so rare, very few doctors have experience diagnosing it.
How Doctors Diagnose AHP
Your doctor will ask about your symptoms and medical history and will examine you. They might also ask if anyone in your family has AHP, although most people with this condition don't have it in their family.
To diagnose AHP, doctors look for three types of symptoms, which doctors call the "classic triad":
- Central nervous system symptoms like anxiety, depression, tiredness, confusion, and seizures
- Peripheral nervous system symptoms like nerve pain and muscle weakness
- Belly pain
A combination of blood, urine, and stool tests can help your doctor confirm the diagnosis. Because AHP is so rare, many labs don't have the right equipment or experience to diagnose it. Your doctor might have to send your test samples to a special lab, and it could take one to two weeks to get your results.
Urine tests
A urine test is often the first test doctors order to diagnose AHP. This test can't confirm that you have the condition, but it's one clue that you might. Urine tests check for these substances:
Aminolaevulinic acid (ALA) and porphobilinogen (PBG). In AHP, your body is missing an enzyme you need to make heme — part of the protein hemoglobin that carries oxygen in your blood. Porphyrins are substances your body uses to make heme. Delta-aminolevulinic acid (ALA) and porphobilinogen (PBG) are ingredients that go into making heme. They're called porphyrin precursors. When your body can't make heme, these materials build up in your body and damage your nerve cells.
When you're having an AHP attack, a urine test will show high levels of ALA and PBG in your urine. Because levels of these substances may be normal even during an attack, your doctor might have to repeat the test more than once.
Creatinine. Your body produces this waste product when it breaks down muscle tissue. High levels of creatinine in your urine can be a sign of AHP.
Blood tests
These are some of the blood tests that help diagnose AHP:
Erythrocyte porphobilinogen deaminase (PBGD). This is one of the enzymes needed to make heme. About 90% of people with AHD will have lower than normal levels. Your PBGD levels can be low even if you don't have symptoms.
Basic metabolic panel (BMP). This test measures levels of substances like calcium, sodium, and potassium in your blood. Low sodium is one sign of AHP.
There are also tests that check for levels of ALA and PBG in your blood.
Genetic testing
For this test, your doctor will send a sample of your blood or saliva to a lab. Genetic tests look for the four gene changes (mutations) that cause AHP:
- ALAD gene: It carries the instructions for making the enzyme aminolevulinate dehydratase.
- CPOX gene: It holds the instructions for making the enzyme coproporphyrinogen oxidase.
- HMBS gene: It provides instructions for making the enzyme hydroxymethylbilane synthase.
- PPOX gene: It carries the instructions for making the protoporphyrinogen oxidase enzyme.
A genetic test confirms the diagnosis. It also shows what type of AHP you have and how severe it is.
If you test positive for AHP, it's important for your close family members (brothers, sisters, and children) to also get tested for the gene mutation. Anyone else in your family who tests positive should see a genetic counselor. The counselor can give them advice on treatments and tips for avoiding things that trigger their attacks.
Show Sources
Photo Credit: Science Photo Library/Getty Images
SOURCES:
American Liver Foundation: "Acute Hepatic Porphyria."
American Porphyria Foundation: "Finding a Doctor."
Cleveland Clinic: "Acute Hepatic Porphyria," "Colitis," "Epilepsy," "Psychosis," "Urinary Tract Infections."
Clinical and Experimental Gastroenterology: "Obstacles to Early Diagnosis of Acute Hepatic Porphyria: Current Perspectives on Improving Early Diagnosis and Clinical Management."
Gastroenterology: "AGA Clinical Practice Update on Diagnosis and Management of Acute Hepatic Porphyrias: Expert Review."
Genetic and Rare Diseases Information Center: "Acute Intermittent Porphyria."
International Foundation for Gastrointestinal Disorders: "Triggers for Acute Attacks in Acute Hepatic Porphyria."
Mayo Clinic: "Appendicitis," "Cholecystitis," "Endometriosis," "Fibromyalgia," "Guillain-Barre Syndrome," "Porphyria."
MedlinePlus: "Basic Metabolic Panel (BMP)."
NHS: "Hepatitis."
Orphanet Journal of Rare Diseases: "Challenges in Diagnosis and Management of Acute Hepatic Porphyrias: From an Uncommon Pediatric Onset to Innovative Treatments and Perspectives."
StatPearls: "Acute Hepatic Porphyria."
American Journal of Medicine: "Acute Porphyrias in the USA: Features of 108 Subjects from Porphyrias Consortium."
