Methylmalonic Acidemia — where the specific gene determines whether vitamin B12 therapy normalizes biochemistry, or whether a lifetime of protein restriction and possible liver transplantation is required.
Whole genome sequencing evaluates all methylmalonic acidemia genes — MUT, MMAA, MMAB, MMACHC, MMADHC — distinguishing B12-responsive from B12-non-responsive forms and determining transplant candidacy.
Methylmalonic Acidemia
Methylmalonic acidemia (MMA) is a group of autosomal recessive organic acidemias caused by impaired conversion of methylmalonyl-CoA to succinyl-CoA in the propionate catabolic pathway. The most severe form is caused by deficiency of methylmalonyl-CoA mutase (MUT gene, chromosome 6p12.3) — the enzyme that requires adenosylcobalamin (vitamin B12) as a cofactor. Additional genes cause MMA through impaired intracellular B12 metabolism: MMAA, MMAB, and MMACHC (the latter also causes combined MMA and homocystinuria, cobalamin C defect). Combined incidence is approximately 1 in 50,000-100,000 births.
MUT-deficient MMA is classified as mut⁰ (no residual enzyme activity, most severe) or mut⁻ (partial residual activity, less severe). MMAA and MMAB variants impair intracellular B12 processing — these patients respond to pharmacological B12 supplementation (hydroxocobalamin injections), which can substantially improve or normalize methylmalonic acid levels. This B12-responsive vs. non-responsive distinction is the most important management classification in MMA. Acute metabolic crises — precipitated by illness, fasting, or protein catabolism — produce metabolic acidosis, hyperammonemia, encephalopathy, and can be fatal. Chronic complications include progressive renal disease, metabolic stroke, optic nerve atrophy, and pancreatitis.
Liver transplantation provides enzyme replacement for the hepatic metabolic defect in MUT-deficient MMA, reducing (but not eliminating) metabolic crisis risk and improving quality of life. Combined liver-kidney transplantation is performed for patients with established renal failure. Gene therapy and mRNA therapy approaches are in clinical development for MUT-deficient MMA — delivering functional MUT mRNA or gene products to restore enzyme activity. Molecular genotyping determines: B12 responsiveness (MMAA/MMAB → responsive; MUT → generally non-responsive), transplant candidacy and urgency, and gene therapy trial eligibility.
MMAA and MMAB variants cause B12-responsive MMA — hydroxocobalamin injections can dramatically reduce methylmalonic acid levels. This is a treatable condition when correctly diagnosed. MUT variants are generally B12-non-responsive.
B12-responsive MMA (MMAA/MMAB) has dramatically better outcomes than MUT-deficient MMA. Newborn screening detects elevated methylmalonic acid but does not identify the gene — molecular diagnosis determines the treatment path.
B12-responsive vs. non-responsive MMA determines whether simple vitamin supplementation or liver transplantation is the treatment path
MMAA-MMA patients treated with regular hydroxocobalamin injections can achieve near-normal methylmalonic acid levels, substantially reducing metabolic crisis risk and renal disease progression. In contrast, MUT mut⁰ patients do not respond to B12 and require strict protein restriction, emergency metabolic protocols, and consideration of liver transplantation for severe recurrent crises. Newborn screening identifies elevated methylmalonic acid but cannot distinguish these categories — molecular genotyping immediately stratifies the patient into the correct treatment pathway.
mRNA therapy in clinical trials targets MUT-deficient MMA — molecular diagnosis determines eligibility for this transformative approach
Systemic mRNA therapy delivering functional MUT mRNA to hepatocytes is in clinical development for mut⁰ and mut⁻ MMA. This approach aims to restore methylmalonyl-CoA mutase activity without liver transplantation. Clinical trial enrollment requires confirmed MUT pathogenic variants — MMAA or MMAB patients are not candidates because their enzyme is functional (the defect is in B12 processing). Molecular genotyping early in life ensures that MUT-deficient patients are identified for current and emerging gene-specific therapies.
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.
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 Methylmalonic Acidemia 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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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
