Test ID: HCASC
Hemochromatosis Cascade
NY State Approved 
Indicates the status of NY State approval and if the test is orderable for NY State clients.
Useful For Suggests clinical disorders or settings where the test may be helpful
Screening to identify those patients who may have or do have hereditary hemochromatosis and are at risk to develop clinical signs and symptoms of the disease
Genetics Test Information Provides information that may help with selection of the correct test or proper submission of the test request
If the ferritin value is abnormal (males >336 mcg/L; females >307 mcg/L) and other causes of an increased value are eliminated (liver disease, etc.), genetic testing for hereditary hemochromatosis (HHEMO/81508 Hemochromatosis HFE Gene Analysis, Blood) should be considered in adults.
Profile Information A profile is a group of laboratory tests that are ordered and performed together under a single Mayo Test ID. Profile information lists the test performed, inclusive of the test fee, when a profile is ordered and includes reporting names and individual availability.
| Test ID | Reporting Name | Available Separately | Always Performed |
|---|---|---|---|
| HCFEC | FE-TIBC, S | Yes, (order FEC) | Yes |
| HCFER | Ferritin, S | Yes, (order FERR) | No |
Testing Algorithm Delineates situation(s) when tests are added to the initial order. This includes reflex and additional tests.
Transferrin saturation is performed first. If elevated (>45%), this will trigger determination of serum ferritin.
See Hereditary Hemochromatosis Algorithm in Special Instructions.
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
Method Name A short description of the method used to perform the test
HCFEC/34625: Photometric, Fe2+-FerroZine Complex
HCFER/23817: Immunoenzymatic Assay
Reporting Name A shorter/abbreviated version of the Published Name for a test; an abbreviated test name
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.
Container/Tube:
Preferred: Serum gel
Acceptable: Red top
Specimen Volume: 1 mL
Collection Instructions:
1. Fasting (12 hours)
2. Draw before 12 noon (preferred).
Additional information:
1. Patient's age and sex are required.
2. Iron-containing supplements should be avoided for 24 hours prior to draw.
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.
Reject Due To Identifies specimen types and conditions that may cause the specimen to be rejected
| Hemolysis | Mild reject; Gross reject |
| Lipemia | NA |
| Icterus | NA |
| Other | NA |
Specimen Stability Information Provides a description of the temperatures required to transport a specimen to the laboratory. Alternate acceptable temperature(s) are also included.
| Specimen Type | Temperature | Time |
|---|---|---|
| Serum | Refrigerated (preferred) | 7 days |
| Frozen | 90 days |
Clinical Information Discusses physiology, pathophysiology, and general clinical aspects, as they relate to a laboratory test
Hereditary hemochromatosis (HH) is an autosomal recessive disorder characterized by increased intestinal absorption of iron with deposition in the liver, pancreas, and multiple other organs. The gene for hemochromatosis was discovered in 1996 and named HFE. Two point mutations were initially described, C282Y and H63D. Approximately 0.5% of Caucasians in the United States are homozygous for C282Y and 10% are heterozygous carriers, confirming that HH is the most common, single-gene inherited disorder in Caucasians.
The initial description of patients with HH was "bronze diabetes" in association with cirrhosis. Currently, most persons diagnosed with HH are asymptomatic. Of those with symptoms, fatigue, arthritis, and impotence are most common. Recent large, population-based screening studies have concluded that most individuals homozygous for C282Y do not develop clinically important disease manifestations. The true penetrance in C282Y homozygotes is unknown.
The diagnosis of HH is based on a combination of clinical, laboratory, and pathological criteria. The best initial test for HH is a fasting, morning transferrin saturation (% saturation). If the transferrin saturation is >45%, it should be repeated along with a serum ferritin. In adults, when both the serum transferrin saturation and ferritin are elevated, the HFE gene test should be performed. Prior to HFE gene testing, a qualified professional should discuss the risks, benefits, and alternatives of genetic testing.
Approximately 85% of US patients with HH are homozygous for C282Y. Absence of the C282Y and H63D mutations does not exclude clinically significant iron overload. HFE gene testing is useful in confirming a diagnosis of HH, screening adult blood relatives of a C282Y homozygous proband, and helping to resolve ambiguous cases of iron overload. A liver biopsy with measurement of the hepatic iron concentration is no longer necessary to confirm the diagnosis in C282Y homozygotes. A liver biopsy also is not necessary in most C282Y homozygotes with serum ferritin values <1,000 mcg/L and normal aspartate aminotransferase values since they have a low risk of having cirrhosis.
Treatment is by phlebotomy. Initially, a pint of blood is removed once per week. The goal is to achieve a serum ferritin of <50 mcg/L. Once depleted of excess iron stores, maintenance phlebotomy approximately every 3 months is usually required. If HH is diagnosed and treated before the development of cirrhosis or diabetes, survival is similar to age- and sex-matched controls without HH. Refer to What's New in Hereditary Hemochromatosis, Mayo Medical Laboratories Communique 2005 April;30(4) for more information regarding diagnostic strategy. See Hereditary Hemochromatosis Algorithm in Special Instructions.
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.
IRON
Males: 50-150 mcg/dL
Females: 35-145 mcg/dL
TOTAL BINDING CAPACITY
250-400 mcg/dL
PERCENT SATURATION
14-50%
FERRITIN
Males: 24-336 mcg/L
Females: 11-307 mcg/L
Interpretation Provides information to assist in interpretation of the test results
A transferrin saturation >45% will trigger the determination of a serum ferritin. If the ferritin value is abnormal (males: >336 mcg/L; females: >307 mcg/L) and other causes of an increased value are eliminated (liver disease, etc.) genetic testing for hereditary hemochromatosis (HHEMO/81508 Hemochromatosis HFE Gene Analysis, Blood) should be considered in adults.
See Hereditary Hemochromatosis Algorithm in Special Instructions.
For more information about hereditary hemochromatosis testing, see Update on Hereditary Hemochromatosis and the HFE Gene in Publications.
Cautions Discusses conditions that may cause diagnostic confusion, including improper specimen collection and handling, inappropriate test selection, and interfering substances
No significant cautionary statements.
Clinical Reference Provides recommendations for further in-depth reading of a clinical nature
1. Tavill AS: Diagnosis and management of hemochromatosis. Hepatology 2001 May;33(5):1321-1328
2. Pietrangelo A: Haemochromatosis. Gut 2003 May;52:23-30
Method Description Describes how the test is performed and provides a method-specific reference
Iron is liberated from transferrin under acidic conditions. Ascorbate reduces the released Fe(3+) ions to Fe(2+) ions, which react with FerroZine to form a colored complex which is measured photometrically at 570 nm. The color intensity is directly proportional to the concentration of iron present.(Package insert: Roche Fe reagend, Roche Diagnostics, Indianapolis, IN, 2010)
Anti-transferrin antibodies react with the antigen in the sample to form an antigen/antibody complex. Following agglutination, this is measured turbidimetrically. Addition of polyethylene glycol (PEG) allows the reaction to progress rapidly to the end point and increases sensitivity.(Package insert: Roche TRSF2 reagent. Indianapolis, IN, 2005). The total iron binding capacity (TIBC) is dependent on transferrin concentration and can be calculated. The percent saturation is calculated using the iron and total iron-binding capacity concentrations by the following equation: % saturation = iron/TIBC x 100.
The ferritin assay is a 2-site immunoenzymatic ("sandwich") assay. A sample is added to a reaction vessel with goat anti-ferritin-alkaline phosphatase conjugate, and paramagnetic particles coated with goat anti-mouse: mouse anti-ferritin complexes. Serum or plasma (heparin) ferritin binds to the immobilized monoclonal anti-ferritin on the solid phase, while the goat anti-ferritin enzyme conjugate reacts with different antigenic sites on the ferritin molecules. After incubation in a reaction vessel, materials bound to the solid phase are held in a magnetic field while unbound materials are washed away. Then, the chemiluminescent substrate Lumi-Phos 530 is added to the vessel and light generated by the reaction is measured with a luminometer. The light production is directly proportional to the concentration of ferritin in the sample. The amount of analyte in the sample is determined from a stored, multipoint calibration curve. The instrument used is a Beckman Coulter Unicel DXI 800.(Package Insert: Beckman Coulter Ireland Inc, Ireland, 2003)
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.
Monday through Sunday; Continuously
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
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.
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.
82728-Ferritin
83540-Iron
83550-Iron binding capacity
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 |
|---|---|---|
| FERR | Ferritin, S | 2276-4 |
| IRON | Iron | 2498-4 |
| TIBC | Total Iron Binding Capacity | 2500-7 |
| SAT | Percent Saturation | 14801-5 |
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