Acute Intermittent Porphyria: Comprehensive information

Porphyrias are metabolic disorders caused by altered activities of enzymes within the heme biosynthetic pathway. Porphyrias can cause neurovisceral manifestations and cutaneous photosensitivity (either chronic and blistering or acute and mostly non-blistering). Heme is essential for the transport of oxygen to cells in the body. If any step in the synthesis of heme is blocked, an intermediate chemical accumulates in the cell, resulting in oxygen depletion. Those intermediate chemicals, known as porphyrins or porphyrin precursors, are the substances of which heme is composed. 

Types of Porphyria

The types of Porphyria are:

• Acute Hepatic Porphyria

1. Acute Intermittent Porphyria
2. ALA dehydratase deficiency Porphyria
3. Hereditary Coproporphyria
4. Variegate Porphyria

• Cutaneous Porphyria

1. Congenital Erythropoietic Porphyria
2. Erythropoietic Porphyria
3. Hepatoerythropoietic Porphyria
4. Porphyria Cutanea Tarda
5. X-linked Protoporphyria

According to the National Institute of Diabetes and Digestive and Kidney Diseases, Acute Intermittent Porphyria is the most common Porphyria. 

Acute Intermittent Porphyria (AIP)

Acute Intermittent Porphyria is a rare inherited metabolic disease due to a deficiency of the hydroxymethylbilane synthase, also known as porphobilinogen deaminase, in heme biosynthesis. AIP manifests after puberty with occasional neuropsychiatric crises associated with the accumulation of porphyrin precursors released from the liver into the circulation. Delays in the diagnosis occur because clinical manifestations are unspecific and commonly mimic acute encephalopathy or abdominal crisis of another origin.  

Symptoms of Acute Intermittent Porphyria

AIP manifests after puberty, especially in women (due to hormonal imbalances). Symptoms usually come as discrete attacks that develop over two or more days.

The common symptoms of AIP are:

• Dysautonomia
• Dark Urine
• Hyponatremia
• Abdominal pain
• Hepatopathy
• Irritability
• Depression
• Seizures
• Anxiety
• Insomnia
• Hallucinations
• Paranoia
• Disorientation, etc.

Diagnosis of AIP

A diagnosis of AIP can be difficult because most symptoms are nonspecific and occur periodically. A diagnosis is usually based on identifying characteristic symptoms from detailed patient history, a thorough clinical evaluation, and specialized tests. 

Clinical Testing and Workup

Healthcare professionals do screening tests to measure the levels of the porphyrin precursor porphobilinogen (PBG) in urine is essential to confirm a diagnosis of acute Porphyria.

Family Testing

The Molecular genetic testing is not essential to confirm a diagnosis as the porphyrin biochemical findings are characteristic. However, molecular genetic testing to detect a mutation in the HMBS gene is usually required so that family members can be offered to test for this mutation.

Treatment of AIP

The treatment of AIP is directed toward the specific symptoms that are apparent in each individual. Treatment may require the coordinated efforts of a team of specialists. Pediatricians, neurologists, hematologists, hepatologists, psychiatrists, and other healthcare professionals may need to systematically and comprehensively plan an affected patient’s treatment.

The treatment objective is to manage symptoms, prevent complications, and suppress heme creation (synthesis) in the liver with hematin, which reduces the production of porphyrin precursors.

• In 2019, the FDA approved Givlaari (givosiran) for treating adult patients with acute hepatic Porphyria, including AIP. Givlaari aims to reduce the number of attacks patients experience.
• Normosang (heme arginate) is another heme preparation that can be used to treat individuals with AIP. 
• Treatment for AIP also includes drugs to treat specific symptoms, such as certain pain medications (analgesics), anti-anxiety drugs, anti-hypertensive drugs, and drugs to treat nausea and vomiting, tachycardia, or restlessness.
• Additional treatment for individuals undergoing an attack includes monitoring fluid and electrolyte balances. 

Statistics and studies

According to the Rare Disease Database, in Europe, the prevalence of symptomatic AIP is reported to be 5.9 per million people in the general population. 

As per the research work of Doctor Dhanpat Kumar Kochar, S.P Medical College, Bikaner (Rajasthan), India, the first case of AIP in India was reported by Wig and Malhotra in 1963 in Bikaner, Rajasthan, and since then, 196 more cases has been reported till date.  

 According to an article published by Apollo medicines, the prevalence in India is unknown due to a lack of extensive studies. The first case of AIP in India was reported in 1954. In a study by Gauri et al. in 1990, 15 patients with AIP were detected out of 2,500 persons of the Maheshwari community surveyed in the Sri-Dungargarh municipal area of Bikaner. 

Most patients become symptomatic at the age of 18-45 years. 

Approved by: Dr. Priyanka                                                                                                         

Source:                                                                            

https://www.apollomedicine.org/article.asp?issn=0976-0016;year=2020;volume=17;issue=2;spage=78;epage=83;aulast=Bhattiprolu

https://rarediseases.org/rare-diseases/acute-intermittent-porphyria/#:~:text=Acute%20intermittent%20porphyria%20(AIP)%20is,porphyrin%20precursors%20in%20the%20body.

https://www.neurologyindia.com/article.asp?issn=0028-3886;year=2007;volume=55;issue=4;spage=413;epage=415;aulast=Kochar