Your child's newborn screening detected elevated phenylalanine. Now the question is which PAH variant is responsible — because the answer determines whether dietary restriction alone is enough, or whether medication can help.
Whole genome sequencing identifies PAH variants that predict BH4 responsiveness — enabling your physician to consider sapropterin therapy that may reduce dietary restriction and improve quality of life.
Phenylketonuria (PKU)
Phenylketonuria (PKU) is an autosomal recessive disorder of phenylalanine metabolism caused by PAH mutations, which encode phenylalanine hydroxylase — the enzyme that converts phenylalanine to tyrosine. Loss-of-function PAH variants impair this critical amino acid conversion, causing phenylalanine accumulation to toxic levels and tyrosine deficiency. Untreated PKU causes severe intellectual disability, behavioral problems, neurological regression, eczema, light skin pigmentation, and a characteristic musty or mousy body odor. However, early treatment with lifelong phenylalanine-restricted diet prevents all manifestations — treated individuals develop normal intelligence and have normal lifespans.
PKU affects approximately 1 in 10,000 to 1 in 15,000 individuals in European populations, with higher prevalence in some Asian and Middle Eastern populations. Over 1,100 PAH variants have been catalogued, showing wide genetic heterogeneity. PKU has been detected via universal newborn screening in all 50 US states since the 1960s — one of the earliest success stories of genetic disease prevention. Critically, approximately 25–50% of PKU patients carry PAH variants that confer BH4 (tetrahydrobiopterin) responsiveness — these individuals can respond to sapropterin (Kuvan), a synthetic BH4 cofactor that enhances residual PAH enzyme activity and may allow significantly less restrictive diets. Genotype-phenotype correlation is strong: specific variant classes (particularly missense mutations maintaining residual activity) respond to BH4, while null variants and frameshift mutations do not.
A PAH variant diagnosis identified at birth through newborn screening mandates immediate dietary intervention with phenylalanine restriction — this prevents intellectual disability and neurological manifestations entirely. Genotype-phenotype correlation directly informs management: BH4-responsive variants may qualify patients for sapropterin therapy, potentially allowing less restrictive diets and improved quality of life compared to lifelong severe phenylalanine restriction. Early treatment is paramount — even brief periods of elevated phenylalanine during the neonatal period can cause permanent cognitive damage. Genetic diagnosis enables carrier screening of family members and preconception counseling for affected individuals planning pregnancy (maternal PKU requiring strict dietary control during pregnancy to prevent fetal damage).
Approximately 25–50% of PKU patients carry BH4-responsive PAH variants that respond to sapropterin therapy, potentially allowing less restrictive diets and improved quality of life.
PAH variant testing is important for predicting BH4 responsiveness and dietary tolerance. Over 1,100 variants exist with strong genotype-phenotype correlation. Genome Test complements, but does not replace, newborn screening.
PAH genotype predicts BH4 responsiveness and dietary flexibility
Although PKU is detected through newborn screening (the standard of care for early detection), genetic testing plays a critical role in predicting BH4 responsiveness and dietary tolerance. Approximately 25–50% of PKU patients carry PAH variants that respond to sapropterin (Kuvan), a BH4 cofactor that enhances residual PAH activity. Specific variant classes — particularly missense mutations maintaining residual enzymatic activity — predict BH4 responsiveness, while null variants and frameshift mutations do not. Over 1,100 PAH variants have been catalogued with strong genotype-phenotype correlation. Whole genome sequencing captures all PAH variants and enables accurate prediction of sapropterin response, confirmed through clinical BH4 loading tests.
Identifying BH4 responsiveness can expand dietary flexibility and quality of life
A PAH variant diagnosis combined with BH4 responsiveness testing can substantially improve quality of life in PKU patients. Lifelong severe phenylalanine restriction is challenging and affects nutrition, social integration, and psychological well-being. BH4-responsive patients may qualify for sapropterin therapy, which can partially normalize phenylalanine metabolism and allow less restrictive diets. This enables greater food choices, improved nutritional status, and better quality of life while maintaining safe phenylalanine levels. Even a modest reduction in dietary restriction can have significant psychosocial benefits. Genetic testing identifies which patients can benefit from this approach.
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 Phenylketonuria (PKU) 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
