Urea Cycle Defects — where hyperammonemia can cause irreversible brain damage within hours, and the specific gene determines protein tolerance, nitrogen scavenger therapy selection, and whether liver transplantation is curative.
Whole genome sequencing evaluates all urea cycle genes — OTC, CPS1, ASS1, ASL, ARG1, NAGS — and distinguishes X-linked OTC deficiency from autosomal recessive defects, enabling accurate genetic counseling and family screening.
Urea Cycle Defects
Urea cycle defects (UCDs) are a group of inherited metabolic disorders caused by deficiency of enzymes or transporters in the urea cycle — the hepatic pathway that converts neurotoxic ammonia to urea for renal excretion. Six primary UCDs are recognized: ornithine transcarbamylase (OTC) deficiency (X-linked, most common, ~50% of all UCDs), carbamoyl phosphate synthetase I (CPS1) deficiency, argininosuccinate synthetase (ASS1) deficiency (citrullinemia type I), argininosuccinate lyase (ASL) deficiency, arginase (ARG1) deficiency, and N-acetylglutamate synthase (NAGS) deficiency. Combined incidence is approximately 1 in 30,000-35,000 births.
UCDs present with hyperammonemia — elevated blood ammonia that is directly neurotoxic. Severe neonatal-onset forms (typically OTC, CPS1, or ASS1 in males with complete enzyme deficiency) present within the first days of life with progressive lethargy, poor feeding, vomiting, hypothermia, and rapid progression to coma and death if untreated. Late-onset forms present with recurrent episodes of hyperammonemia triggered by catabolic stress (illness, surgery, high-protein intake, postpartum period), which can cause encephalopathy, cerebral edema, and progressive cognitive impairment with each episode.
Management includes dietary protein restriction, nitrogen scavenger therapy (sodium benzoate and/or sodium phenylbutyrate/glycerol phenylbutyrate, which provide alternative pathways for nitrogen excretion), essential amino acid supplementation, and emergency hyperammonemia protocols. Liver transplantation is curative for hepatic UCDs (OTC, CPS1, ASS1, NAGS) because the urea cycle is exclusively hepatic — a transplanted liver provides functional enzyme. mRNA therapy delivering functional OTC mRNA to hepatocytes is in clinical trials for OTC deficiency, potentially offering a non-surgical alternative to liver transplantation.
OTC deficiency is X-linked — affected males typically present in the neonatal period, but carrier females can present at any age, often triggered by catabolic stress (illness, surgery, postpartum). Postpartum hyperammonemia in a previously healthy woman should prompt OTC carrier testing.
OTC deficiency is X-linked; other UCDs are autosomal recessive. The inheritance pattern has profound implications for family screening, prenatal diagnosis, and recurrence risk — only molecular diagnosis reliably determines the specific UCD.
Hyperammonemia kills neurons in hours — emergency protocols require knowing the specific UCD for optimal management
Each UCD has a specific biochemical profile that determines the optimal emergency management. ASS1 deficiency (citrullinemia) accumulates citrulline — arginine supplementation is critical. ASL deficiency accumulates argininosuccinic acid — arginine provides both a nitrogen sink and a metabolic substrate. OTC and CPS1 have elevated glutamine rather than citrulline. Nitrogen scavenger selection, dialysis thresholds, and nutritional management all vary by UCD subtype. Molecular diagnosis before the first hyperammonemic crisis enables creation of a gene-specific emergency protocol that reduces brain damage during subsequent episodes.
mRNA therapy for OTC deficiency in clinical trials — molecular confirmation required, and early enrollment maximizes benefit before cumulative brain injury
mRNA therapy delivering functional OTC mRNA via lipid nanoparticles to hepatocytes is in advanced clinical development. This approach could provide OTC enzyme activity without liver transplantation — avoiding the surgical risk, lifelong immunosuppression, and limited organ availability of transplantation. Trial enrollment requires confirmed OTC molecular diagnosis. Early enrollment — before repeated hyperammonemic crises have caused cumulative neurological injury — maximizes the potential cognitive benefit of restoring OTC activity.
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.
Accredited by & published in
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 Urea Cycle Defects 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
- Any country — including virtual groups
- Rare and common conditions covered
Message received.
We'll be in touch within 2 business days. To follow up directly: hello@dantelabs.com
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
