Homocystinuria — where the CBS genotype determines whether the patient responds to vitamin B6 therapy with near-normal outcomes, or requires lifelong methionine-restricted diet and betaine supplementation.
Whole genome sequencing identifies the specific CBS variant — distinguishing pyridoxine (B6)-responsive from non-responsive homocystinuria — the single most important prognostic and treatment distinction in this condition.
Homocystinuria
Classical homocystinuria is an autosomal recessive disorder of methionine metabolism caused by deficiency of cystathionine β-synthase (CBS, chromosome 21q22.3). CBS catalyzes the condensation of homocysteine with serine to form cystathionine — the first step of the transsulfuration pathway. CBS deficiency causes accumulation of homocysteine and methionine in blood and tissues. Homocystinuria affects approximately 1 in 200,000-300,000 births worldwide, with higher prevalence in Ireland (~1 in 65,000) and Qatar (~1 in 1,800). Pyridoxine (vitamin B6) is a cofactor for CBS, and approximately 50% of patients have B6-responsive forms that retain partial CBS activity.
Untreated homocystinuria produces a recognizable clinical syndrome: ectopia lentis (lens dislocation — characteristically downward, distinguishing it from Marfan syndrome where lenses dislocate upward), Marfanoid skeletal features (tall stature, long limbs, pectus deformity, scoliosis), thromboembolism (the leading cause of mortality — elevated homocysteine promotes endothelial damage and coagulation activation), and intellectual disability (variable, ranging from normal intelligence to severe impairment). The thromboembolic risk is lifelong: stroke, pulmonary embolism, and deep vein thrombosis cause significant morbidity and mortality, particularly during surgery, pregnancy, or immobilization.
Treatment depends fundamentally on B6 responsiveness. B6-responsive patients (approximately 50%) are treated with high-dose pyridoxine (100-500mg/day), which enhances residual CBS activity and normalizes or near-normalizes plasma homocysteine levels — these patients have substantially better outcomes including preserved intellect, reduced thromboembolic risk, and often no need for dietary methionine restriction. B6-non-responsive patients require lifelong methionine-restricted diet, betaine supplementation (which provides an alternative route for homocysteine remethylation), folate, and B12. The distinction between responsive and non-responsive forms is the critical management decision and is determined by the specific CBS genotype.
Lens dislocation in homocystinuria is typically downward (inferonasal), while in Marfan syndrome it is upward (superotemporal). Any patient with lens dislocation should have plasma homocysteine measured — this single lab test distinguishes the two conditions.
B6 responsiveness determines the entire treatment approach and long-term prognosis. The CBS genotype predicts responsiveness with high accuracy — enabling immediate treatment optimization rather than months of empirical trial.
B6-responsive CBS variants predict near-normal outcomes — non-responsive variants predict need for lifelong dietary restriction
The CBS variants p.Ile278Thr and p.Ala114Val are associated with B6-responsive homocystinuria and retain meaningful residual enzyme activity. Patients homozygous or compound heterozygous for these variants typically achieve biochemical normalization on pyridoxine therapy alone, with excellent long-term intellectual and vascular outcomes. In contrast, p.Gly307Ser (the most common Irish/European variant) is B6-non-responsive and requires lifelong methionine-restricted diet and betaine. Molecular genotyping provides immediate treatment stratification — rather than the 6-8 week empirical B6 trial that delays definitive management.
Surgical and anesthetic risk is dramatically elevated in undiagnosed homocystinuria — molecular diagnosis prevents perioperative catastrophe
Elevated homocysteine dramatically increases perioperative thromboembolic risk. Undiagnosed homocystinuria patients undergoing surgery — particularly orthopedic procedures, which involve immobilization — are at extreme risk for intraoperative or postoperative stroke, pulmonary embolism, or deep vein thrombosis. Several case reports document perioperative death in previously undiagnosed homocystinuria patients. Molecular diagnosis enables appropriate preoperative homocysteine-lowering therapy, perioperative anticoagulation, and avoidance of nitrous oxide anesthesia (which inhibits methionine synthase and acutely worsens homocysteine levels).
Your full DNA (not just a part of it)
Traditional genetic testing looks at narrow sets of genes, missing most parts of your genome. We sequence your full genome — every gene and every region between genes.
Comprehensive insights and specialized reports
Easy to read and with answers you and your doctor can act on. Not a file to interpret — 200+ clinical reports, organized by category.
Your test becomes more valuable every year
Your DNA does not change, but genome science is accelerating. Every month, new variant-disease associations are discovered. We validate these findings and update your reports automatically. Your test becomes more valuable every year.
The results doctors bring to their hardest cases.
Forty years of uncertainty. One test.
A patient had spent decades in the UK healthcare system without a diagnosis. Dante data, accepted by NHS clinical teams at Queen Elizabeth University Hospital Glasgow, identified Noonan Syndrome and a RUNX1 leukemia-associated variant that had gone undetected. After 40 years, they finally had an answer.
A complete read delivers a complete picture.
A patient came to Dante to investigate periodic paralysis. Reading the complete genome identified a concurrent hereditary cardiac finding — Brugada syndrome — that their doctor confirmed with an ECG. The result also explained a family member's unresolved cardiac history. One test. Every answer in it.
Sequenced in 2019. The data worked in 2021.
Jennifer sequenced her genome with Dante two years before her breast cancer diagnosis. When treatment began, Dante's pharmacogenomics data showed her prescribed chemotherapy would cause serious adverse effects. Her doctor selected an alternative — and she started effective treatment from day one.
Every genetic question deserves a complete answer.
Whether you are searching for answers today or protecting your health for tomorrow, a complete read of your entire genome is the only place to start.
It runs in your family. Now you can know if it runs in your genes.
Your genome contains inherited variants associated with medical conditions like cardiac, cancer, and neurological. We read all of them — with the clinical depth to give the result meaning.
Learn more →When traditional lab tests say you're fine. And you know you're not.
Standard diagnostic tests check for a pre-selected set of answers. We sequence your full DNA — including parts that no test was designed to check. If the answer is in your genome, we will help you find it.
Learn more →Your diagnosis may be right. Your treatment plan may be incomplete.
Your genes determine which treatments are most likely to work — and which are not. We give your doctor the tools and insights to inform your treatment plan.
Learn more →You want to know before something forces the question.
Some people don't wait for a diagnosis or a family history to act. Whole genome sequencing gives you the complete genetic picture now — so you and your doctor can make informed decisions before anything becomes urgent.
Learn more →You already took a DNA test. Here's what it couldn't tell you.
Most consumer DNA tests read less than 0.1% of your genome. We read all of it.
Learn more →Clinical-grade results. Chosen by individuals, trusted by doctors for their most complex cases.
Dante Genome Test helped specialists at a UK national acute hospital in the identification of Noonan Syndrome and a rare leukemia-associated genetic variant that had gone undetected. That result changed the medical care of the patient.
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Common questions about whole genome sequencing.
What is the difference between whole genome sequencing and a targeted genetic test?
Targeted genetic tests — including standard hereditary cancer panels — read a pre-defined list of known variants in a specific set of genes. They are designed to find what they already know to look for. Whole genome sequencing reads your entire genome: all 6 billion base pairs, every gene, every region between genes. A Mayo Clinic study published in JAMA Oncology found that standard testing guidelines missed more than half of patients with inherited cancer mutations. Genome Test does not have a fixed list.
What will I receive when my results are ready?
Your Dante Genome delivers 200+ physician-ready reports organized by clinical category — hereditary cancer, cardiac conditions, rare diseases, pharmacogenomics, carrier status, and more. Reports are delivered to your secure Genome Manager and are formatted for direct clinical use. Your genome data is permanently retained and re-analyzed automatically as science advances.
What happens if a clinically significant variant is found?
If a pathogenic or likely-pathogenic variant is identified, it will be clearly flagged in your physician-ready report with clinical context, published evidence, and recommended next steps. We recommend sharing any clinically significant finding with your physician or a genetic counselor, who can guide decisions about surveillance, risk reduction, or cascade testing for family members.
How is this different from a consumer DNA test like 23andMe or AncestryDNA?
Consumer DNA tests use genotyping chips that read less than 0.1% of your genome — a tiny pre-selected set of common variants. They are optimized for ancestry and population-level traits, not clinical genetic findings. The Dante Genome Test sequences 100% of your genome at 30X coverage, the same standard used in clinical diagnostic settings. The two tests are not comparable in scope, methodology, or clinical utility.
How long does it take to get results, and how are they delivered?
Your collection kit ships within 48 hours of ordering. Once your sample arrives at our CLIA-certified laboratory, sequencing and analysis takes 6–8 weeks. Results are delivered securely to your Genome Manager, where you can access your reports, share them with your physician, and receive automatic updates as new findings are validated against your genome.
We work with patient advocacy groups worldwide.
Dante Labs works with patient advocacy groups of any size — for Homocystinuria and other conditions, rare and common. We support groups in any country, including virtual patient advocacy groups.
We can provide customized reports, group discounts, and packages tailored for your members. Please reach out using the form and we'll be in touch within two business days.
- Custom genomic reports for your members
- Group discounts and tailored packages
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- Rare and common conditions covered
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One test.
A lifetime of answers.
One kit, sent to your home. Your entire genome sequenced at the clinical standard used for diagnostic decisions. 200+ physician-ready reports delivered to your Genome Manager in 6–8 weeks — permanent and updated as science advances.
Ships within 48 hours · Results in 6–8 weeks
