What are the other Names for this Condition? (Also known as/Synonyms)

• AP (Acute Porphyria)

What is Acute Porphyria? (Definition/Background Information)

• Porphyrias are disorders resulting from excess porphyrin buildup in the liver and bone marrow. Manufacturing hemoglobin and related proteins (heme synthesis) involves a class of molecules, called porphyrins. Porphyrias are either inherited or acquired disorder, and are described as acute, chronic, and cutaneous
• Acute Porphyria (AP) is a genetic condition affecting heme metabolism that is seen in children and adults. It presents with symptoms during episodes of acute attacks, which are triggered by certain internal or external factors
• Acute Porphyria consist of the following types:
  • Acute Intermittent Porphyria (AIP): It is the most common type of Acute Porphyria
  • Amino Levulinic Acid Dehydratase Deficiency Porphyria (ALAD Porphyria): It is an extremely rare form of porphyria
  • Hereditary Coproporphyria (HCP): HCP is a rare and acute form of porphyria that presents skin symptoms in addition to acute attacks
  • Variegate Porphyria (VP): It is another acute form of porphyria that presents skin symptoms in addition to acute attacks
• Acute Porphyria may be inherited in an autosomal dominant or autosomal recessive manner, due to certain gene mutations, which causes a defect in heme production in the bone marrow and liver
• During acute attacks (presentation of severe symptoms), the disorder is characterized by severe abdominal pain, constipation or diarrhea, and neurological symptoms that include muscle pain and weakness. Skin associated signs and symptoms are not typically observed in Acute Porphyria, although these are sometimes observed in HCP and VP
• A healthcare provider typically diagnoses this genetic disorder by testing porphyrin levels in urine and blood samples, along-with symptom assessment. During episodes of acute attacks, it can be noted that the urine of the affected individual turns reddish-brown on exposure to sunlight
• The treatments for Acute Porphyria involves removing or treating the triggers causing the condition and symptomatic treatment. It can also involve the administration of glucose and bringing about dietary changes to include more carbohydrates. In many, the symptoms of an acute attack subside on their own
• The prognosis of Acute Porphyria is determined by the specific subtype, the severity of symptoms, and whether complications have developed. In many individuals, the prognosis is good with adequate treatment

Who gets Acute Porphyria? (Age and Sex Distribution)

• The prevalence and demographics of Acute Porphyria depend on the specific subtype of the condition
• The manifestation of symptoms may occur in childhood or adulthood; typically, both male and female genders are affected
• The disorder occurs worldwide without any racial or ethnic bias. The prevalence rate varies for each subtype of Acute Porphyria

What are the Risk Factors for Acute Porphyria? (Predisposing Factors)

• A family history of Acute Porphyria increases the risk of a newborn being diagnosed with the condition, since it is typically an inherited disorder

It is important to note that having a risk factor does not mean that one will get the condition. A risk factor increases one’s chances of getting a condition compared to an individual without the risk factors. Some risk factors are more important than others.

Also, not having a risk factor does not mean that an individual will not get the condition. It is always important to discuss the effect of risk factors with your healthcare provider.

What are the Causes of Acute Porphyria? (Etiology)

Acute Porphyria is caused by mutations on genes that are involved in the production of “heme”. The gene undergoing mutations may be inherited in an autosomal dominant or autosomal recessive manner.

• Heme is a critical component of iron-containing proteins called hemoproteins. Hemoglobin is one such protein, which is the oxygen carrier in blood. Blood, bone marrow, and liver have the most heme protein in them
• The gene mutations cause a decrease in porphyrin metabolism. A compromised porphyrin metabolism causes a buildup of porphyrins in the body. This mutation affects the function of a specific enzyme, which disrupts the multistep-wise process of generating heme
• However, this does not manifest as symptoms, since the body can manage with reduced enzyme function to some extent. But, the presence of other internal or external factors may hinder its function further resulting in an acute attack (severe symptoms)

The external factors or triggers may include:

• Environmental stimuli
• Eating an unusual diet, starving
• Illegal drug abuse
• Alcoholism
• Use of certain medications

The internal factors may include:

• Emotional or psychological stress
• Menstruation in women
• Any illness or infection
• Other hormonal factors

Autosomal dominant: Autosomal dominant conditions are traits or disorders that are present when only one copy of the mutation is inherited on a non-sex chromosome. In these types of conditions, the individual has one normal copy and one mutant copy of the gene. The abnormal gene dominates, masking the effects of the correctly function gene. If an individual has an autosomal dominant condition, the chance of passing the abnormal gene on to their offspring is 50%. Children, who do not inherit the abnormal gene, will not develop the condition or pass it on to their offspring.

Autosomal recessive: Autosomal recessive conditions are traits or disorders that occur when two copies of an abnormal gene have been inherited on a non-sex chromosome. If both parents have an autosomal recessive condition, there is a 100% likelihood of passing on the mutated genes to their children. If, however, only one mutant copy of the gene is inherited, the individual will be a carrier of the condition, but will not be present with any symptoms. Children born to two carriers, have a 25% chance of being homozygous dominant (unaffected), a 50% chance of being heterozygous (carrier), and a 25% chance of being homozygous recessive (affected).

What are the Signs and Symptoms of Acute Porphyria?

The various signs and symptoms of Acute Porphyria are the result of porphyrin buildup in the body. These may be mild or severe and vary from one individual to another. The signs and symptoms may include:

• Stomach pain and cramping abdominal pain
• Diarrhea or constipation
• Retention of urine
• Neurological signs and symptoms may include:
  • Peripheral neuropathy
  • Muscular pain and weak muscles
  • If the respiratory muscles are affected, it may cause breathing difficulties
  • Seizures in some cases
• When the nervous system of the internal organs is affected, it gives rise to neurovisceral crises
• Psychiatric signs and symptoms may include:
  • Change in sensation
  • Feeling confused
  • Hallucinating
• Abnormal color of urine (reddish) on exposure to sunlight; which tends to resolve following treatment, or when the symptoms go away
• When liver involvement is present, yellowing of skin and eyes may be observed
• Cutaneous signs and symptoms are observed in VP and HCP and may include:
  • Skin gets burnt on sun exposure resulting in blister formation
  • The skin becomes weak and fragile over time
  • Change of skin pigmentation and thickening

How is Acute Porphyria Diagnosed?

The diagnosis of Acute Porphyria is made by the following tools:

• A complete physical examination and an assessment of symptoms
• An evaluation of the affected individual’s full medical history
• Measurement of the porphyrin levels in blood, urine, or feces
  • Urine screening test (24 hours)
  • Assessment of blood levels of PBG and ALA
• Measurement of activity of the involved enzyme
• Molecular genetic testing before or after birth, to confirm gene mutation

Many clinical conditions may have similar signs and symptoms. Your healthcare provider may perform additional tests to rule out other clinical conditions to arrive at a definitive diagnosis.

What are the possible Complications of Acute Porphyria?

The potential complications of Acute Porphyria may include:

• Severe pain and emotional stress during periods of acute attacks
• Cosmetic issues due to skin of the face, neck, arms being chronically affected in Variegate Porphyria or Hereditary Coproporphyria
• Anemia and related conditions, due to low levels of oxygen transport
• Increased heart rate and increased blood pressure may be the outcome of autonomic nervous system being affected
• If the neuroendocrine region of brain is affected, it can lead to hyponatremia and hypomagnesemia (low sodium and magnesium levels in blood respectively), resulting in additional complications
• The affected individuals are vulnerable to hepatocellular carcinoma (HCC); hence, they should be periodically monitored

How is Acute Porphyria Treated?

The treatment measures for Acute Porphyria is based on the specific subtype of the condition. It may include:

• When the first signs of disease are recognized, the individual is given oral/intravenous glucose (called glucose loading) and a carbohydrate-rich diet
• Medications to control severity of the acute attacks
• Large dose and strong painkillers (narcotic analgesics or opiates) may be given for severe pain
• Antipsychotic medication (chlorpromazine) to treat some of the neurological symptoms, antidepressants for depression
• Beta-blockers, such as propanalol, for cardiovascular conditions (such as hypertension and tachycardia)
• Anti-seizure medications (such as gabapentin) for seizure
• Blood disorder medications (intravenous heme) may be used to treat accumulation of porphyrin compounds
• Individuals undergoing regular blood removal as part of treatment (therapeutic phlebotomy) for decreasing iron buildup, should take plenty of fluids including juice or milk
• If the symptoms are because of normal menstrual cycles, birth control hormonal pills or synthetic peptide drugs may be helpful
• Skin protection by avoiding direct sunlight and use of topical sunscreen creams, for skin symptoms
• Blood transfusions, based on the severity of anemia
• A splenectomy (removal of the spleen) to alleviate bleeding and worsening anemia (due to spleen enlargement)
• Bone marrow transplant for severe cases
• Liver transplantation for liver failure may be recommended by the healthcare provider

In many individuals, the symptoms of an acute attack subside on their own. Sometimes, it may be severe as to requiring treatment in a hospital setting. The treatment also involves removing or treating any internal or external triggers.

How can Acute Porphyria be Prevented?

• Currently, there are no specific methods or guidelines to prevent Acute Porphyria, since it is a genetic condition
• Genetic testing of the expecting parents (and related family members) and prenatal diagnosis (molecular testing of the fetus during pregnancy) may help in understanding the risks better during pregnancy
• If there is a family history of the condition, then genetic counseling will help assess risks, before planning for a child
• Active research is currently being performed to explore the possibilities for treatment and prevention of inherited and acquired genetic disorders such as Acute Porphyria

Regular medical screening at periodic intervals with tests and physical examinations are highly recommended.

Once the triggers or precipitating factors for Acute Porphyria are identified, certain steps may be taken to avoid them to the extent possible, such as:

• Having a healthy lifestyle and a regular diet
• Stress avoidance, when possible
• Avoid the use of illegal drugs; avoiding alcohol
• Discontinuing medicines that trigger Acute Porphyria, instead using alternatives
• Undertaking prompt treatment for any illness or infection

Individuals with Acute Porphyrias are encouraged to wear an emergency (medical) identification tag or suitable bracelet to inform providers/others about their condition, which is particularly helpful in case of an acute attack.

What is the Prognosis of Acute Porphyria? (Outcomes/Resolutions)

• The prognosis of Acute Porphyria depends on the type of porphyria and varies with the severity of the condition. But, it is generally good for mild cases and the symptoms go away with adequate treatment
• If neurological symptoms are severe and involve the muscle and sensory faculties, then recovery may be prolonged and it may even take many months

Additional and Relevant Useful Information for Acute Porphyria:

When there is a mild to moderate increase in urine porphyrin levels following the use of certain medications, exposure to some chemicals, or due to liver or bone marrow disorders, the condition is termed secondary porphyrinuria. These are often confused as ‘true’ porphyrias due to the set of similar presentations they are observed to have.