Quantitative measurement of 3-O-methyldopa from dried blood spot for screening of aromatic L-amino acid decarboxylase (AADC) deficiency — a rare but treatable neurotransmitter disorder. Performed by high-performance liquid chromatography coupled with tandem mass spectrometry (LC-MS/MS).
3-O-Methyldopa (3-OMD)
3–5 working days
This method screens for aromatic L-amino acid decarboxylase (AADC) deficiency, a rare autosomal recessive neurotransmitter disorder affecting the synthesis of dopamine, serotonin, and other critical catecholamines. The test quantifies 3-O-methyldopa (3-OMD) from a dried blood spot, which accumulates when AADC enzyme activity is impaired.
AADC deficiency is profoundly important to identify because eladocagene exuparvovec (Upstaza) — a recently approved gene therapy — is now available as a disease-modifying treatment. Early diagnosis enables access to this transformative therapy and prevents years of disability.
Clinical presentations of AADC deficiency include:
Critically, AADC deficiency is frequently misdiagnosed as cerebral palsy, epilepsy, autism spectrum disorder, or idiopathic developmental delay, leading to years of missed opportunities for effective treatment. A simple DBS biomarker test can fundamentally change a patient's clinical trajectory.
Aromatic L-amino acid decarboxylase (AADC) is a pyridoxal phosphate-dependent enzyme encoded by the DDC gene. It catalyses two essential metabolic steps: the conversion of L-DOPA to dopamine in the catecholamine synthesis pathway, and the conversion of 5-hydroxytryptophan (5-HTP) to serotonin in the serotonin synthesis pathway. AADC also participates in the synthesis of histamine and trace amines. Thus, AADC deficiency causes simultaneous depletion of dopamine, serotonin, and other neurotransmitters critical for motor control, mood regulation, and autonomic function.
Eladocagene exuparvovec (Upstaza) received regulatory approval from the EMA and FDA, offering the first disease-modifying treatment
Symptoms mimic cerebral palsy, epilepsy, and autism, resulting in many patients going undiagnosed for years
A single 3-OMD measurement from a heel prick can identify affected individuals and enable early access to therapy
Mutations in the DDC gene impair AADC protein synthesis or function, leading to reduced enzyme activity. In affected individuals, neurotransmitter precursors (L-DOPA and 5-HTP) accumulate and are shunted into alternative metabolic pathways. One major pathway is methylation by catechol-O-methyltransferase (COMT), producing 3-O-methyldopa. This accumulation makes 3-O-methyldopa an excellent biomarker for AADC deficiency: blood levels are dramatically elevated in affected individuals and normal in unaffected controls.
Differential diagnosis includes other causes of neurotransmitter disorders such as PNPO (pyridoxal phosphate oxidase) deficiency, various B6-responsive conditions, monoamine oxidase deficiencies, and vesicular monoamine transporter defects. However, AADC deficiency can be specifically identified through 3-OMD measurement combined with evaluation of other neurotransmitter metabolites (biopterin, homovanillic acid, 5-hydroxyindoleacetic acid) by expanded metabolomics.
The availability of gene therapy has transformed AADC deficiency from a progressive neurodevelopmental disorder into a treatable condition. Gene therapy restores AADC enzyme expression in the central nervous system, enabling normalisation of dopamine and serotonin synthesis. Early treatment, particularly in infants identified through expanded newborn screening, has demonstrated the capacity to prevent neurological deterioration and enable normal or near-normal development.
3-O-methyldopa is extracted from dried blood spots and quantified by high-performance liquid chromatography coupled to tandem mass spectrometry (LC-MS/MS). The assay uses stable isotope-labelled internal standard to correct for variation in extraction efficiency and ionisation. The method is highly sensitive, with the ability to detect even modest elevation in 3-OMD levels that may distinguish heterozygous carriers from affected individuals in some cases.
3-O-methyldopa is a stable metabolite that does not degrade significantly in dried blood spots at ambient temperature, making DBS collection ideal for newborn screening and population-based testing. The dried format enables convenient home-based collection and postal transit without loss of analytical sensitivity.
Dried blood spot collection from a heel prick is rapid, minimally invasive, and suitable for all ages including newborns. Samples are stable at room temperature during collection, transport, and storage, facilitating integration into universal newborn screening programmes and point-of-care testing systems.
From enquiry to results in a few simple steps — no clinic visit required.
This test is available to healthcare professionals, wellness brands, clinics, and research institutions worldwide. We currently serve partners in:
Whether you need testing services for your patients, white-label kits for your brand, or method transfer to your own laboratory — get in touch to discuss how we can work together.
AADC deficiency is a rare autosomal recessive disorder affecting the synthesis of dopamine, serotonin, and other catecholamines. It is caused by mutations in the DDC gene, which encodes the aromatic L-amino acid decarboxylase enzyme. The condition is often misdiagnosed as cerebral palsy or epilepsy, leading to years of missed treatment opportunities.
The test measures 3-O-methyldopa (3-OMD) from a dried blood spot using LC-MS/MS. When AADC enzyme activity is impaired, the neurotransmitter precursor L-DOPA cannot be converted to dopamine and is instead methylated to 3-OMD, which accumulates to dramatically elevated levels. An elevated result triggers further confirmatory testing including enzyme activity assay and genetic analysis.
A simple finger-prick is used to collect a few drops of blood onto a dried blood spot (DBS) card. The method is suitable for newborns (heel prick) and older patients alike. No venous blood draw is required, and the sample can be collected at home or in a clinical setting.
Results are typically delivered within 3 to 5 working days from the time your sample arrives at our laboratory. The analysis is performed by LC-MS/MS, which provides highly sensitive and specific quantification of 3-O-methyldopa.
Gene therapy (eladocagene exuparvovec / Upstaza) is now available as a disease-modifying treatment for AADC deficiency. Early diagnosis before irreversible neurological damage occurs dramatically improves outcomes. Delayed diagnosis means missed treatment windows, as the therapy is most effective when administered early in the disease course.
Masdiag's 3-O-methyldopa screening test is available worldwide through our partner network. We currently serve healthcare professionals, screening programmes, and clinics in Europe, the United Kingdom, Asia, Australia, New Zealand, and the United States. Contact us to discuss testing services or integration into your screening programme.
Whether you need testing services, method transfer, or white-label kit development — we'd love to hear from you.