Niemann-Pick Disease — a family of lysosomal storage disorders where type C masquerades as psychiatric illness, progressive ataxia, or dementia in adults for an average of 7 years before the genetic diagnosis is made.
Whole genome sequencing evaluates SMPD1 (types A and B) and NPC1/NPC2 (type C) simultaneously — identifying treatable NPC1/NPC2 variants in adults presenting with vertical gaze palsy, cerebellar ataxia, or early-onset cognitive decline.
Niemann-Pick Disease
Niemann-Pick disease (NPD) encompasses genetically and clinically distinct lysosomal storage disorders. Types A and B are caused by pathogenic variants in SMPD1 (sphingomyelin phosphodiesterase 1) on chromosome 11p15.4, encoding acid sphingomyelinase; their deficiency causes sphingomyelin accumulation in macrophages of the liver, spleen, lung, and brain. Type A is a severe infantile neurodegenerative condition with death by age 3; type B is an attenuated form with primarily visceral involvement and variable neurological features, with survival into adulthood. Type C Niemann-Pick disease is caused by variants in NPC1 (95%) or NPC2 (5%) on different chromosomes — these encode proteins mediating intracellular cholesterol transport — and is pathophysiologically and clinically distinct from types A and B.
Niemann-Pick type C (NPC) is arguably the most diagnostically challenging lysosomal storage disorder. In the adolescent and adult-onset forms — which account for approximately 50% of all NPC cases — the presentation mimics common neurological and psychiatric conditions: vertical supranuclear gaze palsy (VSGP — a nearly pathognomonic finding for NPC but often unrecognized), cerebellar ataxia, dystonia, dysarthria, dysphagia, cognitive decline, and psychiatric symptoms including psychosis, depression, and anxiety. The mean time from symptom onset to NPC diagnosis in adolescent/adult-onset cases is approximately 4-7 years, during which patients may receive misdiagnoses of multiple sclerosis, spinocerebellar ataxia, bipolar disorder, or schizophrenia.
Miglustat (Zavesca), a substrate reduction therapy, is approved in Europe for NPC neurological stabilization — it slows the rate of neurological progression and is most effective when initiated early in the disease course. Arimoclomol, a heat shock protein amplifier, is in late-stage clinical development for NPC. These disease-modifying therapies make molecular diagnosis of NPC directly therapeutic — a confirmed NPC1 or NPC2 pathogenic variant qualifies the patient for miglustat and for arimoclomol trial enrollment. In types A/B, olipudase alfa (Xenpozyme), an enzyme replacement therapy, was approved for non-neurological manifestations of acid sphingomyelinase deficiency in 2022.
Very late-onset NPC (age >40) may present as an atypical dementia or frontotemporal dementia-like syndrome. NPC should be considered in any adult under 60 with vertical gaze palsy, unexplained cerebellar ataxia, or early cognitive decline accompanied by splenomegaly.
SMPD1 and NPC1/NPC2 are distinct genes requiring different tests. Plasma oxysterol biomarkers screen for NPC but are not specific — molecular confirmation requires complete NPC1 and NPC2 sequencing. Whole genome sequencing evaluates all Niemann-Pick genes simultaneously.
Vertical gaze palsy in a young adult is virtually pathognomonic for NPC — but NPC confirmation requires molecular testing
Vertical supranuclear gaze palsy — reduced or absent voluntary vertical eye movement — is the single most distinctive clinical feature of NPC and is rarely seen in other conditions. Combined with cerebellar ataxia, cognitive decline, and a history of prolonged neonatal jaundice or childhood splenomegaly, it should prompt immediate NPC evaluation. Plasma oxysterol measurement (24S-hydroxycholesterol, 25-hydroxycholesterol, 7-ketocholesterol) provides a sensitive screening biomarker but is not specific. Confirmatory molecular diagnosis requires complete sequencing of NPC1 (42 exons) and NPC2, genes that have no hotspot and require full-gene analysis. Whole genome sequencing provides this simultaneously.
Miglustat therapy requires confirmed molecular diagnosis — and should begin as early in NPC neurological disease as possible
Miglustat's effect in NPC is one of slowing progression — it does not reverse neurological damage already sustained. Clinical trial data and registry studies consistently show that earlier initiation of miglustat therapy in the neurological disease course is associated with better preservation of neurological function. Every year of diagnostic delay in adult-onset NPC is a year of neurological damage accumulation before treatment can begin. Confirming the NPC1 or NPC2 molecular diagnosis is the prerequisite for miglustat initiation — a symptom-based diagnosis alone is not sufficient for drug approval in most jurisdictions. Whole genome sequencing reduces time to molecular confirmation.
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 Niemann-Pick Disease 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
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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
