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Acute Intermittent Porphyria via the HMBS Gene

Summary and Pricing

Test Method

Exome Sequencing with CNV Detection
Test Code Test Copy GenesTest CPT Code Gene CPT Codes Copy CPT Codes Base Price
HMBS 81406 81406,81479 $990
Test Code Test Copy Genes Test CPT Code Gene CPT Codes Copy CPT Code Base Price
8229HMBS81406 81406,81479 $990 Order Options and Pricing

Pricing Comments

Our favored testing approach is exome based NextGen sequencing with CNV analysis. This will allow cost effective reflexing to PGxome or other exome based tests. However, if full gene Sanger sequencing is desired for STAT turnaround time, insurance, or other reasons, please see link below for Test Code, pricing, and turnaround time information. If the Sanger option is selected, CNV detection may be ordered through Test #600.

An additional 25% charge will be applied to STAT orders. STAT orders are prioritized throughout the testing process.

Click here for costs to reflex to whole PGxome (if original test is on PGxome Sequencing platform).

Click here for costs to reflex to whole PGnome (if original test is on PGnome Sequencing platform).

The Sanger Sequencing method for this test is NY State approved.

For Sanger Sequencing click here.

Turnaround Time

3 weeks on average for standard orders or 2 weeks on average for STAT orders.

Please note: Once the testing process begins, an Estimated Report Date (ERD) range will be displayed in the portal. This is the most accurate prediction of when your report will be complete and may differ from the average TAT published on our website. About 85% of our tests will be reported within or before the ERD range. We will notify you of significant delays or holds which will impact the ERD. Learn more about turnaround times here.

Targeted Testing

For ordering sequencing of targeted known variants, go to our Targeted Variants page.


Genetic Counselors


  • Luke Drury, PhD

Clinical Features and Genetics

Clinical Features

Acute Intermittent porphyria (AIP) is a metabolic disorder due to impairment of the third enzyme, porphobilinogen (PBG) deaminase, in the heme biosynthetic pathway. AIP is the most common form of acute porphyria affecting about 1 in 10,000 Swedish, 3 in 100,000 Finnish, and 5-10 in 100,000 US individuals. It is characterized by intermittent attacks of neurological dysfunction including severe abdominal pain, neuropsychiatric symptoms, nausea, vomiting, tachycardia and hypertension. Acute, life-threatening, attacks may be provoked by certain drugs, stress, infections, alcohol, caloric restriction, or endocrine factors with bouts typically resolving within two weeks. Symptom onset primarily occurs during the third and fourth decades of life with women being more susceptible to attacks, although some individuals with AIP may remain asymptomatic throughout life (Whatley and Badminton 1993). Pre-symptomatic diagnosis of AIP is helpful in preventing acute attacks through avoidance of certain triggers highlighted above. Biochemical analysis showing elevated PBG and aminolevulinic acid (ALA) levels in urine are primary indicators for AIP but may appear normal during asymptomatic phases. Impaired erythrocyte PBGD activity is also a hallmark of AIP, but is also seen in patients with anemia, liver disease, uremia, chronic polyarthritis, and malignancies. Genetic testing has been shown helpful in diagnosis of AIP during asymptomatic phases and in differential diagnosis (Puy et al. 1997; Kauppinen and Fraunberg 2002).


AIP is primarily inherited in an autosomal dominant manner through mutations in the HMBS gene with incomplete penetrance. Individuals homozygous for HMBS mutations have also been reported in a few cases with severe AIP presenting before two years of age (Solis et al. 2004). Missense, splice site alterations, nonsense, and small insertions/deletions represent 45%, 18%, 15%, and 22% of causative variants for AIP with about half occurring within exons 10-14 (Puy et al. 1997; Kauppinen and Fraunberg 2002; Yang et al. 2008). Large deletions have been reported in a few cases (Whatley et al. 2009). The HMBS gene encodes porphobilinogen (PGB) deaminase which is the third enzyme involved in the heme biosynthetic pathway. Causative variants primarily lead to premature protein termination or destabilization leading to decreased PGB deaminase levels and activity (Whatley and Badminton 1993; Bustad et al. 2013).

Clinical Sensitivity - Sequencing with CNV PGxome

In patients with decreased PBG deaminase activity indicative of AIP, underlying mutations in the HMBS gene were detected in 240 of 252 individuals (Puy et al. 1997). Analytical sensitivity for detection of causative mutations in the HMBS gene is >95% as large deletions are present in only a few cases (Whatley et al. 2009).

Testing Strategy

This test provides full coverage of all coding exons of the HMBS gene plus 10 bases of flanking noncoding DNA in all available transcripts along with other non-coding regions in which pathogenic variants have been identified at PreventionGenetics or reported elsewhere. We define full coverage as >20X NGS reads or Sanger sequencing. PGnome panels typically provide slightly increased coverage over the PGxome equivalent. PGnome sequencing panels have the added benefit of additional analysis and reporting of deep intronic regions (where applicable).

Dependent on the sequencing backbone selected for this testing, discounted reflex testing to any other similar backbone-based test is available (i.e., PGxome panel to whole PGxome; PGnome panel to whole PGnome).

Indications for Test

Patients with symptoms consistent with AIP and biochemical analysis indicating elevated urinary PBG and ALA levels or decreased erythrocyte PBG deaminase activity are primary indicators for disease. With patients being asymptomatic between attacks, urinary PGB and ALA levels may appear normal.


Official Gene Symbol OMIM ID
HMBS 609806
Inheritance Abbreviation
Autosomal Dominant AD
Autosomal Recessive AR
X-Linked XL
Mitochondrial MT


Name Inheritance OMIM ID
Acute Intermittent Porphyria AD 176000


  • Bustad HJ, Vorland M, Rønneseth E, Sandberg S, Martinez A, Toska K. 2013. Conformational stability and activity analysis of two hydroxymethylbilane synthase mutants, K132N and V215E, with different phenotypic association with acute intermittent porphyria. Bioscience Reports 33: 617–626. PubMed ID: 23815679
  • Kauppinen R, Fraunberg M von und zu. 2002. Molecular and biochemical studies of acute intermittent porphyria in 196 patients and their families. Clinical chemistry 48: 1891–1900. PubMed ID: 12406973
  • Puy H, Deybach JC, Lamoril J, Robreau AM, Silva V Da, Gouya L, Grandchamp B, Nordmann Y. 1997. Molecular epidemiology and diagnosis of PBG deaminase gene defects in acute intermittent porphyria. The American Journal of Human Genetics 60: 1373–1383. PubMed ID: 9199558
  • Solis C, Martinez-Bermejo A, Naidich TP, Kaufmann WE, Astrin KH, Bishop DF, Desnick RJ. 2004. Acute intermittent porphyria: studies of the severe homozygous dominant disease provides insights into the neurologic attacks in acute porphyrias. Arch. Neurol. 61: 1764-1770. PubMed ID: 15534187
  • Whatley SD, Badminton MN. 1993. Acute Intermittent Porphyria. In: Pagon RA, Adam MP, Ardinger HH, Bird TD, Dolan CR, Fong C-T, Smith RJ, and Stephens K, editors. GeneReviews(®), Seattle (WA): University of Washington, Seattle. PubMed ID: 20301372
  • Whatley SD, Mason NG, Woolf JR, Newcombe RG, Elder GH, Badminton MN. 2009. Diagnostic Strategies for Autosomal Dominant Acute Porphyrias: Retrospective Analysis of 467 Unrelated Patients Referred for Mutational Analysis of the HMBS, CPOX, or PPOX Gene. Clinical Chemistry 55: 1406–1414. PubMed ID: 19460837
  • Yang C-C, Kuo H-C, You H-L, Wang J, Huang C-C, Liu C-Y, Lan M-Y, Stephenson DA, Lee M-J. 2008. HMBS Mutations in Chinese Patients with Acute Intermittent Porphyria. Annals of Human Genetics 72: 683–686. PubMed ID: 18627369


Ordering Options

We offer several options when ordering sequencing tests. For more information on these options, see our Ordering Instructions page. To view available options, click on the Order Options button within the test description.

myPrevent - Online Ordering

  • The test can be added to your online orders in the Summary and Pricing section.
  • Once the test has been added log in to myPrevent to fill out an online requisition form.
  • PGnome sequencing panels can be ordered via the myPrevent portal only at this time.

Requisition Form

  • A completed requisition form must accompany all specimens.
  • Billing information along with specimen and shipping instructions are within the requisition form.
  • All testing must be ordered by a qualified healthcare provider.

For Requisition Forms, visit our Forms page

If ordering a Duo or Trio test, the proband and all comparator samples are required to initiate testing. If we do not receive all required samples for the test ordered within 21 days, we will convert the order to the most effective testing strategy with the samples available. Prior authorization and/or billing in place may be impacted by a change in test code.

Specimen Types

Specimen Requirements and Shipping Details

PGxome (Exome) Sequencing Panel

PGnome (Genome) Sequencing Panel

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Note: acceptable specimen types are whole blood and DNA from whole blood only.
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