HMBS Gene, Known Mutation
NY State Approved Indicates the status of NY State approval and if the test is orderable for NY State clients.
Diagnostic confirmation of hydroxymethylbilane synthase (HMBS) deficiency when a familial mutation has been previously identified
Carrier screening of at-risk individuals when a mutation in the HMBS gene has been identified in an affected family member
Genetics Test Information Provides information that may help with selection of the correct test or proper submission of the test request
Documentation of the specific familial mutation(s) must be provided with the specimen in order to perform this test.
Reflex Tests Lists test(s) that may or may not be performed, at an additional charge, depending on the result and interpretation of the initial test(s)
|Test ID||Reporting Name||Available Separately||Always Performed|
|FBC||Fibroblast Culture for Genetic Test||Yes||No|
Testing Algorithm Delineates situation(s) when tests are added to the initial order. This includes reflex and additional tests.
If skin biopsy is received, fibroblast culture will be added and charged separately.
Special Instructions and Forms Describes specimen collection and preparation information, test algorithms, and other information pertinent to test. Also includes pertinent information and consent forms to be used when requesting a particular test
Polymerase Chain Reaction (PCR) Amplification/DNA Sequencing
(PCR is utilized pursuant to a license agreement with Roche Molecular Systems, Inc.)
Reporting Name A shorter/abbreviated version of the Published Name for a test; an abbreviated test name
HMBS Gene, Known Mutation
Acute intermittent porphyria
Specimen Type Describes the specimen type needed for testing
Specimen Required Defines the optimal specimen. This field describes the type of specimen required to perform the test and the preferred volume to complete testing. The volume allows automated processing, fastest throughput and, when indicated, repeat or reflex testing.
1. Molecular Genetics-Biochemical Disorders Patient Information Sheet (Supply T527) in Special Instructions
2. New York Clients-Informed consent is required. Please document on the request form or electronic order that a copy is on file. An Informed Consent for Genetic Testing (Supply T576) is available in Special Instructions.
Specimen must arrive within 96 hours of collection.
Submit only 1 of the following specimens:
Specimen Type: Blood
Preferred: Lavender top (EDTA) or yellow top (ACD)
Acceptable: Any anticoagulant
Specimen Volume: 3 mL
1. Invert several times to mix blood.
2. Send specimen in original tube.
Specimen Stability Information: Ambient (preferred)/Refrigerated
Specimen Type: Cultured fibroblasts
Container/Tube: T-75 or T-25 flask
Specimen Volume: 1 full T-75 or 2 full T-25 flasks
Specimen Stability Information: Ambient (preferred)/Refrigerated <24 hours
Specimen Type: Skin biopsy
Container/Tube: Sterile container with any standard cell culture media (eg, minimal essential media, RPMI 1640). The solution should be supplemented with 1% penicillin and streptomycin. Tubes can be supplied upon request (Eagle's minimum essential medium with 1% penicillin and streptomycin [Supply T115]).
Specimen Volume: 4-mm punch
Specimen Stability Information: Refrigerated (preferred)/Ambient
Specimen Type: Blood spot
Container/Tube: Whatman Protein Saver 903 Paper
Specimen Volume: 5 blood spots
1. Let blood dry on the filter paper at ambient temperature in a horizontal position for 3 hours.
2. Do not expose specimen to heat or direct sunlight.
3. Do not stack wet specimens.
4. Keep specimen dry.
Specimen Stability Information: Ambient (preferred)/Refrigerated
Specimen Minimum Volume Defines the amount of specimen required to perform an assay once, including instrument and container dead space. Submitting the minimum specimen volume makes it impossible to repeat the test or perform confirmatory or perform reflex testing. In some situations, a minimum specimen volume may result in a QNS (quantity not sufficient) result, requiring a second specimen to be collected.
Blood: 1 mL; Blood Spots: 3
Plasma or serum
Specimen Stability Information Provides a description of the temperatures required to transport a specimen to the laboratory. Alternate acceptable temperature(s) are also included.
Clinical Information Discusses physiology, pathophysiology, and general clinical aspects, as they relate to a laboratory test
Hydroxymethylbilane synthase (HMBS) deficiency is an autosomal dominant disorder with incomplete penetrance that can present as acute intermittent porphyria (AIP). The most common clinical presentation of AIP is abdominal pain. Acute attacks can include vomiting, diarrhea, constipation, urinary retention, acute episodes of neuropathic symptoms, psychiatric symptoms, seizures, respiratory paralysis, tachycardia, and hypertension. Respiratory paralysis can progress to coma and death. HMBS deficiency can also be without clinical or biochemical manifestations.
Acute attacks may be prevented by avoiding both endogenous and exogenous triggers. These triggers include porphyrogenic drugs, hormonal contraceptives, fasting, alcohol, tobacco, and cannabis.
The measurement of porphobilinogen deaminase (PBG-D) enzyme activity in erythrocytes facilitates detection of AIP during latent periods, and also confirms a biochemical diagnosis during acute episodes. However, a normal result does not completely exclude a diagnosis of HMBS deficiency/AIP. The preferred diagnostic test is molecular genetic testing of the HMBS gene.
Reference Values Describes reference intervals and additional information for interpretation of test results. May include intervals based on age and sex when appropriate. Intervals are Mayo-derived, unless otherwise designated. If an interpretive report is provided, the reference value field will state this.
An interpretive report will be provided
An interpretive report will be provided.
Cautions Discusses conditions that may cause diagnostic confusion, including improper specimen collection and handling, inappropriate test selection, and interfering substances
The identification of a disease-causing mutation in an affected family member is necessary before predictive testing for other family members can be offered. If a familial mutation has not been previously identified, order HMBSS/61216 HMBS Gene, Full Gene Analysis.
Analysis is performed for the familial mutation provided only. This assay does not rule-out the presence of other mutations in this gene or in other genes that may be associated with acute intermittent porphyria.
Test results should be interpreted in the context of clinical findings, family history, and other laboratory data. Any error in the diagnosis or in the pedigree provided to us, including false-paternity, could lead to erroneous interpretation of results.
A previous bone marrow transplant from an allogenic donor will interfere with testing. Call Mayo Medical Laboratories at 1-800-533-1710 for instructions for testing patients who have received a bone marrow transplant.
Clinical Reference Provides recommendations for further in-depth reading of a clinical nature
1. Thunell S: Hydroxymethylbilane Synthase Deficiency. In GeneReviews (Internet). Edited by RA Pagon, TD Bird, CR Dolan, K Stephens. University of Washington, Seattle WA; 1993-2005 Sep27 (updated 2011 Sep 01)
2. Siegesmund M, van Tuyll van Serooskerken AM, Poblete-Gutierrez P, Frank J: The acute hepatic porphyrias: current status and future challenges. Best Pract Res Clin Gastroenterol 2010 Oct;24(5):593-605
3. Anderson KE, Bloomer JR, Bonkovsky HL, et al: Recommendations for the diagnosis and treatment of the acute porphyrias. Ann Intern Med 2005 Mar 15;142(6):439-450
Method Description Describes how the test is performed and provides a method-specific reference
DNA sequence analysis is performed to test for the presence of a specific mutation in the HMBS gene that was previously identified in a family member.(Unpublished Mayo method)
Day(s) and Time(s) Test Performed Outlines the days and times the test is performed. This field reflects the day and time the sample must be in the testing laboratory to begin the testing process and includes any specimen preparation and processing time required before the test is performed. Some tests are listed as continuously performed, which means assays are performed several times during the day.
Analytic Time Defines the amount of time it takes the laboratory to setup and perform the test. This is defined in number of days. The shortest interval of time expressed is "same day/1 day," which means the results may be available the same day that the sample is received in the testing laboratory. One day means results are available 1 day after the sample is received in the laboratory.
Maximum Laboratory Time Defines the maximum time from specimen receipt at Mayo Medical Laboratories until the release of the test result
Specimen Retention Time Outlines the length of time after testing that a specimen is kept in the laboratory before it is discarded
Whole Blood: 2 weeks (if available) Extracted DNA: 3 months
Performing Laboratory Location The location of the laboratory that performs the test
Test Classification Provides information regarding the medical device classification for laboratory test kits and reagents. Tests may be classified as cleared or approved by the US Food and Drug Administration (FDA) and used per manufacturer's instructions, or as products that do not undergo full FDA review and approval, and are then labeled as an Analyte Specific Reagent (ASR), Investigation Use Only (IUO) product, or a Research Use Only (RUO) product.
This test was developed and its performance characteristics determined by Mayo Clinic in a manner consistent with CLIA requirements. This test has not been cleared or approved by the U.S. Food and Drug Administration.
CPT Code Information Provides guidance in determining the appropriate Current Procedural Terminology (CPT) code(s) information for each test or profile. The listed CPT codes reflect Mayo Medical Laboratories interpretation of CPT coding requirements. It is the responsibility of each laboratory to determine correct CPT codes to use for billing.
81479-Unlisted molecular pathology procedure
LOINC® Code Information Provides guidance in determining the Logical Observation Identifiers Names and Codes (LOINC) values for the result codes returned for this test or profile.
|Result ID||Reporting Name||LOINC Code|
|33681||Reason for Referral||N/A|