Shedding Light on Acute Intermittent Porphyria: Understanding, Diagnosing, and Using Genetic Testing

Expert Reviewed By: ⁠Dr. Brandon Colby MD

Acute Intermittent Porphyria (AIP) is a rare genetic disorder that affects the production of heme, a component of hemoglobin. This nonerythroid variant of porphyria is caused by mutations in the HMBS gene, which encodes for the enzyme hydroxymethylbilane synthase. This enzyme plays a crucial role in the heme biosynthesis pathway, and its deficiency leads to the accumulation of toxic porphyrin precursors in the body. AIP can cause a wide range of symptoms, including abdominal pain, muscle weakness, and neurological issues. Early diagnosis and prompt treatment are essential for managing AIP and preventing complications. In this article, we will explore the importance of understanding, diagnosing, and using genetic testing for AIP.

Understanding Acute Intermittent Porphyria

AIP is an autosomal dominant disorder, meaning that an affected individual has a 50% chance of passing the condition to their offspring. The severity of symptoms can vary greatly among individuals, with some experiencing mild or no symptoms at all, while others may have severe, life-threatening episodes. The exact cause of this variability is still unclear, but it is thought to be influenced by genetic and environmental factors.

Recent research has expanded our understanding of the genetic basis of AIP. A study identified a new classical splicing variant, c.912 + 1G>C, in the HMBS gene, which is pathogenic and provides crucial information for genetic diagnosis. Another case report of a 14-year-old female with severe AIP symptoms highlights the importance of early diagnosis and prompt treatment.

Diagnosing Acute Intermittent Porphyria

Diagnosing AIP can be challenging due to the wide range of symptoms and their similarity to other conditions. A letter to the editor discusses a case of MELAS syndrome, a mitochondrial disorder, which mimicked AIP, emphasizing the need for differential diagnosis. AIP diagnosis typically involves a combination of clinical evaluation, biochemical testing, and genetic testing.

Using Genetic Testing for Diagnosis

Genetic testing can be a valuable tool for diagnosing AIP, as it can identify pathogenic variants in the HMBS gene. This can help confirm the diagnosis, especially in cases where biochemical testing results are inconclusive or the clinical presentation is atypical. Genetic testing can also be useful for identifying asymptomatic carriers of the HMBS gene mutation, allowing for early intervention and management of potential triggers.

Managing Acute Intermittent Porphyria

Once diagnosed, the management of AIP involves avoiding triggers, such as certain medications, alcohol, and fasting, as well as treating acute attacks promptly. In some cases, intravenous hemin therapy may be used to reduce the production of toxic porphyrin precursors. Early diagnosis and prompt treatment are essential for preventing complications and improving the quality of life for individuals with AIP.

Genetic Testing for Family Members

As AIP is an inherited disorder, genetic testing can also be beneficial for family members of affected individuals. Identifying carriers of the HMBS gene mutation can help them make informed decisions about family planning and take appropriate precautions to avoid potential triggers.

Mortality in Acute Intermittent Porphyria

A study examining mortality in pedigrees with AIP found that mortality from HMBS variant heterozygosity is not increased compared to the general population. However, severe excess mortality occurred in young women and old men between 1915 and 1964. This highlights the importance of continued research and improved management strategies for AIP to reduce the risk of complications and improve outcomes for affected individuals.

Conclusion

Understanding, diagnosing, and using genetic testing for Acute Intermittent Porphyria is crucial for the effective management of this rare genetic disorder. Early diagnosis and prompt treatment can significantly improve the quality of life for individuals with AIP and their families. Genetic testing can aid in the diagnostic process, help identify asymptomatic carriers, and provide valuable information for family planning and management of potential triggers.

About The Expert Reviewer

Dr. Brandon Colby MD is a US physician specializing in the personalized prevention of disease through the use of genomic technologies. He’s an expert in genetic testing, genetic analysis, and precision medicine. Dr. Colby is also the Founder of  and the author of ⁠⁠Outsmart Your Genes.

Dr. Colby holds an MD from the Mount Sinai School of Medicine, an MBA from Stanford University’s Graduate School of Business, and a degree in Genetics with Honors from the University of Michigan. He is an Affiliate Specialist of the American College of Medical Genetics and Genomics (⁠⁠ACMG), an Associate of the American College of Preventive Medicine (⁠⁠ACPM), and a member of the National Society of Genetic Counselors (⁠NSGC)