Expert Reviewed By: Dr. Brandon Colby MD
Understanding Acute Hepatic Porphyria
Acute hepatic porphyria (AHP) is a group of rare, inherited metabolic disorders characterized by a deficiency of enzymes involved in heme biosynthesis. This deficiency leads to the accumulation of porphyrins and porphyrin precursors, which can cause a range of symptoms, including abdominal pain, nausea, vomiting, and neurological complications. The disease burden of AHP is considerable, as evidenced by the ENVISION trial, which showed that patients with AHP experience significant physical and emotional impacts on their well-being, regardless of the frequency of attacks or the use of prophylactic treatments like hemin or glucose.
Diagnosing Acute Hepatic Porphyria
Diagnosing AHP can be challenging due to the overlap of symptoms with other conditions, such as cyclic vomiting syndrome. A recent study investigated the prevalence of undiagnosed AHP in patients with cyclic vomiting syndrome and found that there is a significant overlap in clinical symptoms between the two conditions. This highlights the importance of considering AHP as a potential diagnosis in patients presenting with symptoms that may be indicative of the disorder.
Diagnosis of AHP typically involves a combination of biochemical tests, including measuring the levels of porphyrins and porphyrin precursors in urine, blood, and feces. Confirmatory testing involves the identification of specific enzyme deficiencies through enzyme assays or genetic testing.
Genetic Testing for Acute Hepatic Porphyria
Genetic testing can play a crucial role in the diagnosis and management of AHP, as it can help identify the specific type of porphyria and provide information on the inheritance pattern of the disorder. Genetic testing can also be useful for family members of individuals diagnosed with AHP, as it can help determine their risk of developing the condition or passing it on to their offspring.
Uses of Genetic Testing in Diagnosis
Genetic testing can confirm the diagnosis of AHP by identifying mutations in the genes responsible for the disorder. In the case of acute hepatic porphyria, digenic, mutations in the HMBS and ALAD genes are involved. Identifying these mutations can help determine the specific type of AHP and guide appropriate treatment strategies.
Uses of Genetic Testing in Family Members
For family members of individuals diagnosed with AHP, genetic testing can provide valuable information about their risk of developing the disorder or passing it on to their children. By identifying whether a family member carries a mutation in one or both of the genes associated with AHP, genetic testing can help inform decisions about family planning and guide appropriate monitoring and management strategies for at-risk individuals.
Uses of Genetic Testing in Treatment
Genetic testing can also play a role in guiding treatment strategies for AHP. For example, the RNA interference therapeutic givosiran has been shown to alleviate some of the disease burden associated with AHP, as evidenced by the ENVISION trial. However, a recent study found that givosiran treatment may exacerbate dysregulated homocysteine metabolism in AHP patients, although there is no proof of correlations between hyperhomocysteinemia and changes in givosiran's efficacy or safety. Genetic testing can help identify patients who may be at risk for this complication and inform decisions about the use of givosiran in their treatment plan.
Conclusion
Understanding, diagnosing, and utilizing genetic testing for acute hepatic porphyria is essential for managing this rare and complex disorder. Genetic testing can confirm the diagnosis, inform family planning decisions, and guide treatment strategies, ultimately improving the quality of life for those affected by AHP. As research continues to advance our understanding of the genetic underpinnings of AHP and the development of new treatments, the role of genetic testing in the diagnosis and management of this disorder is likely to become even more critical.
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)