OdysseyDx™

Rare Disease Solutions

Unraveling Rare Disease Mysteries

Grasping the genomics of rare diseases enables medical professionals to identify the sources of previously undiagnosed conditions, sparing families from lengthy hospital visits and superfluous tests. Over 7,000 rare diseases are currently recognized, with new ones emerging annually. Combined, these conditions affect 2-6% of the global population, or over 150 million individuals. ^1–3 The so-called “diagnostic odyssey” for rare diseases typically lasts 5 to 7 years, involving up to 8 physicians and 2 to 3 misdiagnoses. ^4,5 As 80% of rare diseases are genetic or possess a genetic component, comprehensive genomic sequencing holds significant promise for uncovering the underlying causes in patients. Next-generation sequencing (NGS) provides the greatest probability for diagnosing rare diseases and offers the quickest route to concluding the diagnostic odyssey. ^6-8

The Value of Genomics in Diagnosing Rare Diseases

Genomics plays a crucial role in transforming the approach to rare disease diagnosis, shifting from symptom evaluation to examining molecular origins. Gaining insight into the biological foundations of these conditions can lead to improved care and tailored treatments, supported by evidence-based outcomes. Such molecular diagnoses in the realm of rare disease genomics form the foundation for precision medicine. Identifying the molecular cause of a rare disease is a vital step with far-reaching benefits for patients, their families, physicians, and other healthcare providers. The American College of Genetics and Genomics (ACMG) asserts that determining the genetic basis of an individual’s condition holds value for the patient, their family, and society as a whole. ⁹

Many Different Variant Types are Pathogenic for Rare Disease Cases 

Advantages of Rare Disease Genomics

TAILORED DISEASE MANAGEMENT: Comprehending the mechanisms of rare diseases enables physicians to direct patients to the right specialists, select personalized treatments, and provide condition-specific follow-up.
REDUCED EXPENSES: By circumventing extended diagnostic journeys, genomic diagnoses for rare diseases can prevent expensive tests and procedures while minimizing unnecessary referrals.
INFORMED FAMILY PLANNING: Determining the inheritance pattern of a rare disease offers insight into recurrence risks for patients and their families, facilitating knowledgeable family planning decisions.
PSYCHOSOCIAL BENEFITS: Beyond reducing stress linked to diagnostic odysseys, obtaining a molecular diagnosis connects affected families with rare disease support groups, fostering a sense of community.
WIDER SOCIETAL IMPACT: Delving into the genomics of rare diseases can help identify novel drug targets and enhance the effectiveness of care.

Rare Disease Patient Stories

Ending Carson & Chase’s 6-Year Diagnostic Odyssey

Initially, Carson received a cerebral palsy diagnosis, but his brother Chase’s condition revealed this to be incorrect. After another four years, whole-genome sequencing successfully identified the true diagnosis for both Carson and Chase: mitochondrial enoyl CoA reductase protein-associated neurodegeneration (MEPAN).

Donovan’s Journey to Diagnosis

Donovan’s range of symptoms pointed to over 20 possible conditions and nearly a dozen medical specialties. After a 6-year search, whole-genome sequencing detected a variant in the SKI gene, ultimately leading to a diagnosis of Shprintzen-Goldberg syndrome.

Sample Preparation Instructions

All clinical materials should be collected with approved methods to avoid contamination and cross contamination. A sterile environment must be maintained when collecting samples. Our sample preparation requirements are detailed in the table below:

EDTA Blood	≥ 1 mL
Buccal swab	1 Oragene™ OCR-100 buccal swab collection set
Saliva	1 Oragene™ OG-610 saliva collection set
Ready to use DNA	≥ 1 µg For DNA samples, we recommend extraction using Qiagen kits, elution in water in 20 µL volume (min), plus evaluation of 260/280 Ratio (1.6 - 2.1) and fluorescent dye quantification of concentration (> 10 ng/µL) before sending.

Sample Transport

EDTA Blood, buccal swab, saliva and DNA samples can be sent via regular mail at room temperature. Liquid blood is stable for up to 4 days during transport.

Shipping Instructions

Sample should be sent to:

AGTC Genomics Sdn Bhd (1428365-D)
J2-1, Pusat Perdagangan Bukit Jalil,
Jalan Persiaran Jalil 1,
Bukit Jalil,
57000 Kuala Lumpur,
Malaysia

References

1. Nguengang Wakap, S., Lambert, D.M., Olry, A. et al. Estimating cumulative point prevalence of rare diseases: analysis of the Orphanet database. Eur J Hum Genet. 2020;28:165–173. https://doi.org/10.1038/s41431-019-0508-0
2. Ferreira CR. The burden of rare diseases. Am J Med Genet A. 2019;179(6):885-892. doi:10.1002/ajmg.a.61124
3. Walker CE, Mahede T, Davis G, et al. The collective impact of rare diseases in Western Australia: an estimate using a population-based cohort. Genet Med. 2017;19(5):546-552. doi:10.1038/gim.2016.143
4. Global Commission to End the Diagnostic Odyssey for Children with a Rare Disease. 2019.
5. Rare Disease Impact Report: Insights from patients and the medical community. globalgenes.org/wp-content/uploads/2013/04/ShireReport-1.pdf.
6. Bick D, Jones M, Taylor SL, Taft RJ, Belmont J. Case for genome sequencing in infants and children with rare, undiagnosed or genetic diseases. J Med Genet. 2019;56(12):783-791. doi:10.1136/jmedgenet-2019-106111.
7. Clark MM, Stark Z, Farnaes L, et al. Meta-analysis of the diagnostic and clinical utility of genome and exome sequencing and chromosomal microarray in children with suspected genetic diseases. NPJ Genom Med. 2018;3:16. https://doi.org/10.1038/s41525-018-0053-8
8. Vissers LE, Gilissen C, Veltman JA. Genetic studies in intellectual disability and related disorders. Nat Rev Genet. 2016;17(1):9-18. doi:10.1038/nrg3999
9. ACMG Board of Directors. Clinical utility of genetic and genomic services: a position statement of the American College of Medical Genetics and Genomics. Genet Med. 2015;17(6):505-507. doi:10.1038/gim.2015.41