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Complementary Genetic Testing & Counseling Pilot Program for Atypical Hemolytic Uremic Syndrom (Atypical-HUS)
Pilot Program Tests & Services
This is sponsored, no charge genetic testing and counseling, for a limited time period in the United States (US).
The atypical-HUS Complimentary Prognostic Genetic Testing Pilot Program offers high-quality, disease-specific genetic testing and genetic counseling services to those diagnosed with atypical-HUS to help inform on long-term prognosis, monitoring, and management decisions.
This pilot program was created to provide equal access to up-to-date and high-quality genetic testing and counseling to all atypical-HUS patients to help them make more informed decisions about their health with their medical provider.
- Genetic counselors will be available before or after genetic testing to explain or review genetic test results with individuals and families to support them in assessing prognosis based on results.
- Pre- and/or post-test clinical consultations between the ordering healthcare provider and geneticists will be made available as needed.
- Genetic test consultations are provided to support healthcare providers through understanding the tests being done, aid in interpreting results, and provide result-specific insights regarding variants and genes. The geneticist can also provide insights into publications, relevant studies, and patient resources.
- ADAMTS13, C2, C3, C3AR1, C4BPA, C4BPB, CD46 (MCP), CFB, CFH, CFHR1, CFHR2, CFHR3, CFHR4, CFHR5, CFI, DGKE, INF2, MMACHC, PLG, THBD, VTN and WT1, plus the region of C5 underlying poor response to eculizumab and a specific, gain-of-function intronic variant (c.914-5T>A) in TSEN2 linked to aHUS. In addition to picking up both known and novel single nucleotide variants, this test also detects the large deletions in CFHR3-1 and CFHR1-4.
- CFH region deletion and duplication analysis by MLPA when indicated.
- Regular turnaround (5 days).
- Outbound draw kits with sample requirements and a prepaid return shipping label to be sent to physicians or patients as needed.
Key: ADAMTS13, a disintegrin and metalloproteinase with thrombospondin type 1 motif, 13; C2, complement component 2; C3, complement component 3; C3AR1, complement component 3a receptor 1; C4BPA, complement component 4 binding protein alpha; CD46, cluster of differentiation 46; CFB, complement factor B gene; CFH, complement factor H gene; CFHR1, complement factor H-related 1; CFHR1-4, complement factor H-related genes 1-4; CFHR2, complement factor H-related 2; CFHR3, complement factor H-related 3; CFHR3-1, complement factor H-related genes 3-1; CFHR4, complement factor H-related 4; CFHR5, complement factor H-related 5; CFI, complement factor I gene; DGKE, diacylglycerol kinase-ε; INF2, inverted formin 2; MLPA, multiplex ligation-dependent probe amplification; MMACHC, metabolism of cobalamin associated C; PLG, plasminogen; THBD, thrombomodulin gene; TSEN2, tRNA splicing endonuclease subunit 2; VTN, vitronectin; MCP, membrane cofactor protein gene; WT1, Wilms' tumor 1 gene.
atypical-HUS, atypical hemolytic uremic syndrome.
Eligibility & Enrollment
Eligibility Criteria:
To be eligible for the atypical-HUS Complimentary Prognostic Genetic Testing Pilot Program, patients must meet the criteria below:
Diagnosed with atypical-HUS by way of ICD-10 code D59.39- Had ADAMTS13 activity testing completed and thrombotic thrombocytopenic purpura (TTP) ruled out
- Ordering physician's practice must be in New York, California, Florida, or Texas
- Patients must consent
The following patients are NOT eligible if:
This program will be limited to one test per patient. Familial testing will not be offered as part of the pilot program.
Diagnosis as STEC-HUS at time of TMA presentation, without a diagnosis of atypical-HUS- Patients not agreeing to consent
ICD-10, International Classification of Diseases Tenth Revision; STEC-HUS, Shiga toxin-producing Escherichia coli-associated hemolytic uremic syndrome; TMA, Thrombotic microangiopathy.
Enrollment & Program Logistics:
1
Online, paper, or phone enrollment options are available. To enroll a patient via phone, call Machaon Client Services at the number below. Prior to specimen collection, please ensure all eligibility criteria are satisfied.
(800) 566-3462
2
Buccal swab or blood collection kits containing instructions and a prepaid return postage label can be sent. Additionally, 1 mL to 3 mL of ethylenediamine tetraacetic acid (EDTA) whole blood can be drawn (lavender top tubes). Please call Machaon Client Services for proper specimen collection, shipping requirements, and a prepaid return shipping label.
3
The patient’s specimen should be packaged along with the enrollment form and sent to Machaon Client Services using the prepaid return shipping label.
4
Receive results based on the preferred method determined during the enrollment process. Clinical consultation services and genetic counseling can be scheduled as needed.
What is Atypical-HUS?
Atypical-HUS is a life-threatening condition with continuous risk of complement-mediated thrombotic microangiopathy (TMA), characterized by microangiopathic hemolytic anemia, thrombocytopenia, and organ damage.2,3 Atypical-HUS develops as a result of exposure to factors or conditions that trigger complement overactivation, and/or a patient’s genetic predisposition to complement dysregulation.2-4
For optimal patient outcomes, early recognition and appropriate management are critical to reduce the risk of irreversible organ damage or death.2 If left undiagnosed, atypical-HUS has a high degree of morbidity and mortality.3 Outcomes for patients with atypical-HUS receiving plasma exchange/plasma infusion are poor; 56% of adults progress to end-stage kidney disease (ESKD) or die within 1 year, and up to 70% with certain mutations have ESKD or die within 3 years.5,6
Atypical-HUS remains a clinical diagnosis.7 About 40% of patients with atypical-HUS do not have an identified genetic mutation, hence genetic testing for diagnosis has limitations.3,8 As mutations continue to be discovered, some of these individuals may prove to have a genetic component.9,10
How Can Genetic Testing Help Inform Prognosis?
While detection of a genetic variant has limitations, it can provide guidance around the management of disease and prognosis. Patients with atypical-HUS carrying certain genetic mutations experience poorer prognoses.11 Patients with identified mutations are associated with a higher risk of TMA recurrence, ESKD progression, and death within the next year after the first episode.8,12
The risk of TMA recurrence is increased after a renal transplant with certain mutations.7,11 Clinical outcomes of unmanaged patients with atypical-HUS carrying identified genetic mutations are outlined in the following chart.11
| Gene | Risk of death or ESKD within the next year after first episode | Risk of aHUS recurrence | Risk of aHUS recurrence after renal transplant |
|---|---|---|---|
|
CFH or CFH-CFHR1/3 hybrid genes
|
50%-70% | 50% | 75%-90% |
|
MCP single
|
0%-6% | 70%-90% | <20% |
|
Anti-FH
|
30%-40% | 40%-60% | Higher with increased antibody titers |
|
CFI
|
50% | 10%-30% | 45%-80% |
|
C3
|
60% | 50% | 40%-70% |
|
THBD
|
50% | 30% | ? |
|
CFB
|
50% | 100% | 100% |
Key: aHUS, atypical hemolytic uremic syndrome; Anti-FH, anti-complement factor H antibodies; C3, complement component 3; CFB, complement factor B gene; CFH, complement factor H gene; CFHR, complement factor H-related genes; CFI, complement factor I gene; ESKD, end-stage kidney disease; MCP, membrane cofactor protein gene; THBD, thrombomodulin gene.
Adapted from Abbas F, et al. World J Transplant. 2018;8(5):122-141 and Campistol JM, et al. Nefrologia. 2015;35(5):421-447.
Atypical-HUS, atypical hemolytic uremic syndrome.
Aside from genetics, it is recommended to also assess the patient's family history of TMA, current renal status, and other risk factors of TMA, such as pediatric onset or pregnancy, to appropriately define prognosis.12
Learn more: ahussource.com/physician/
The information in this presentation is intended as education information for healthcare professionals. It does not replace a healthcare professional’s judgment or clinical diagnosis.
Program Disclosures
-
While the Alexion Rare Disease Unit provides financial support for this program, tests and services are performed by independent third parties. -
Healthcare professionals must confirm that patients meet specific criteria to use the program. -
Alexion receives de-identified data from this program, but at no time does Alexion receive patient-identifiable information.a Alexion will treat this aggregated, non-patient-identifiable information in accordance with its privacy policy, available at: https://alexion.com/Legal#privacynotice. -
Both genetic testing and genetic counseling are available as part of this program. -
Healthcare professionals or patients who use this program have no obligation to recommend, purchase, order, prescribe, promote, administer, use, or support any Alexion product. -
No patients, healthcare professionals, or payers, including government payers, are billed for this program.
a. Alexion may use healthcare professional contact information for research purposes.