Research shows that HMBS mutations are estimated to occur in approximately 1 in 1700 caucasians (there is not enough data in other populations) while AIP symptoms are shown to be present in approximately 1 in 200,000 caucasians. It can be inferred that the penetrance of AIP is approximately 1% of the HMBS heterozygous community, concluding that there are other factors needed to induce AIP symptoms. Variants of AIP
There have been more than 400 mutations in the heme biosynthesis identified to cause AIP. In the erythroid variant, mutations in the exon 1 sequence of the housekeeping gene, splicing of exon 1, and splicing of exon 3 causes an alternative form of AIP wherein there is decreased activity of the liver enzyme but erythroid cells have regular activity. HMBS has two isoforms, housekeeping and erythroid. Additionally, there is also the non-erythroid variant of AIP in which there are mutations in exons 3-15 and there is decreased activity in both isozymes. Most individuals with AIP have mutations in exons 3–15. Loss of function mutations of HMBS cause decreased activity of the enzymes normally present. Diagnosis
The initial diagnosis of acute porphyria is confirmed by urinalysis, including the common method, the Watson-Schwartz test. Elevated urine porphobilinogen confirms diagnosis of AIP, hereditary coproporphyria (HCP), or variegate porphyria (VP). A positive test should be indicated with an increase of five times normal, not just a slight increase which can occur with dehydration.
To distinguish between AIP from HCP and VP, fecal porphyrin levels are normal in AIP but elevated in HCP and VP.Rapid, accurate diagnosis is important. Delays in diagnosis may result in permanent neurological damage or death. Diagnosis with Genetic Testing
With advancement and increased accessibility to genetic testing and follow up counseling, the morbidity of AIP has decreased because of early diagnosis. The combination of targeted mutation analysis and biochemical activity tracking have provided positive results for identifying the risk of AIP development. Mutation analysis has a 95% sensitivity and a 100% specificity for confirmation of pathogenicity of a mutation. Genetic testing can detect AIP in patients with symptoms that would have otherwise gone undiagnosed or misdiagnosed. The biochemical analysis route of detection is slightly less accurate compared to genetic testing, which has 84% sensitivity and 71% specificity, but is still chosen over other alternatives and can provide some of the predictive information that genetic testing does. Patients diagnosed with genetic testing at the asymptomatic stage were less likely to develop symptoms throughout their life. Additionally, individuals who were diagnosed at the symptomatic stage encountered more mild attacks after diagnosis, although they still had symptoms. Genetic testing availability has decreased the rate of patients seeking treatment by medical staff, as patients experiencing less severe symptoms instead opt to self treat at home. Treatment
If drugs have caused the attack, discontinuing the offending substances is essential. A high-carbohydrate (10% glucose) infusion is recommended, which may aid in recovery.