Pompe Disease — a progressive muscle glycogen storage disorder with effective enzyme replacement therapy, where an average 7-year diagnosis delay in adults allows irreversible respiratory and motor muscle damage to accumulate before treatment begins.
Whole genome sequencing reads the complete GAA gene, identifying all variant types including the common intronic pseudodeficiency allele that confounds enzyme assay-based carrier and newborn screening in Pompe disease.
Pompe Disease
Pompe disease (glycogen storage disease type II, GSDII, acid maltase deficiency) is an autosomal recessive lysosomal storage disorder caused by pathogenic variants in GAA (acid alpha-glucosidase) on chromosome 17q25.3. GAA encodes the enzyme responsible for lysosomal glycogen degradation; its deficiency leads to progressive glycogen accumulation in muscle cells, causing skeletal muscle weakness, respiratory failure, and cardiac involvement. Pompe disease presents as a clinical spectrum ranging from classic infantile-onset Pompe disease (IOPD) — characterized by rapidly progressive hypertrophic cardiomyopathy, profound hypotonia, and respiratory failure in the first months of life — to late-onset Pompe disease (LOPD), presenting from early childhood to the eighth decade with progressive proximal muscle weakness and respiratory insufficiency without cardiac involvement.
The molecular genetics of Pompe disease are complex. Over 900 GAA variants have been documented. The most common disease-causing variant in individuals of European ancestry is c.-32-13T>G (IVS1), a leaky splice site variant that allows approximately 10-20% normal GAA mRNA production and is associated with late-onset disease. The most common pathogenic variant in African-ancestry patients is p.Arg854X. A critical molecular complexity is the GAA pseudodeficiency allele (c.1726G>A; p.Gly576Ser and c.2065G>A; p.Glu689Lys, usually in cis forming the c.[1726G>A;2065G>A] haplotype), which reduces GAA enzyme activity on biochemical assay without causing disease. This pseudodeficiency allele confounds newborn screening programs and carrier assays, creating false-positive results that require molecular confirmation to resolve.
Alglucosidase alfa (Myozyme/Lumizyme) has been the standard enzyme replacement therapy (ERT) for Pompe disease since 2006 and substantially slows progression, particularly in LOPD patients treated before irreversible muscle loss. In 2022, cipaglucosidase alfa (Pombiliti) combined with miglustat (a pharmacological chaperone) received FDA approval, demonstrating superiority to standard alglucosidase alfa in LOPD in the PROPEL trial. Gene therapy approaches using AAV vectors are in clinical trials. The window of maximum treatment benefit in LOPD is early in the disease course — before diaphragmatic and limb-girdle muscle fibrosis develops — making early molecular diagnosis critical.
Classic infantile Pompe and late-onset Pompe are phenotypically distinct. The IVS1 (c.-32-13T>G) variant allows some residual GAA expression and is strongly associated with late-onset disease. Compound heterozygotes for IVS1 plus a null allele have variable but typically late-onset presentations.
The GAA pseudodeficiency allele causes false-positive results on enzyme assays and newborn screens. Only molecular genotyping can distinguish true Pompe disease from pseudodeficiency — and the complete GAA genotype determines which ERT protocol is optimal.
Pseudodeficiency alleles cause false-positive Pompe screening results that only molecular testing can resolve
Newborn screening programs that detect low acid alpha-glucosidase (GAA) enzyme activity on dried blood spots generate false-positive results in infants who carry one or two GAA pseudodeficiency alleles — alleles that reduce enzyme activity on assay without causing disease. The pseudodeficiency allele (c.[1726G>A;2065G>A]) is present in approximately 3-4% of the general population and is particularly common in Asian ancestry groups. Distinguishing a true Pompe disease newborn from a pseudodeficiency-positive newborn requires molecular GAA genotyping. Whole genome sequencing identifies all GAA variants including the pseudodeficiency haplotype, resolving ambiguous newborn screen results and preventing both over-treatment of pseudodeficiency carriers and under-treatment of true Pompe disease cases.
The cipaglucosidase alfa + miglustat combination has variant-specific response characteristics
Cipaglucosidase alfa (Pombiliti) is a next-generation recombinant GAA with improved mannose-6-phosphate receptor-mediated uptake and superior muscle delivery compared to standard alglucosidase alfa. Miglustat co-administration stabilizes the enzyme during blood transit. Clinical trial data from PROPEL showed overall superiority to standard ERT, with the greatest benefit in patients who had not previously been on ERT and those with higher anti-drug antibody titers. The GAA genotype — particularly whether a patient has residual GAA mRNA production (such as IVS1/null compound heterozygotes) — influences anti-drug antibody development risk, which is a key determinant of ERT response. Complete GAA characterization informs this immune response risk prediction.
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.
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Easy to read and with answers you and your doctor can act on. Not a file to interpret — 200+ clinical reports, organized by category.
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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.
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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.
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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.
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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
