{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,7]],"date-time":"2026-10-07T10:49:37Z","timestamp":1791370177622,"version":"4.3.1"},"reference-count":10,"publisher":"SMC Media","issue":"10","license":[{"start":{"date-parts":[[2026,9,4]],"date-time":"2026-09-04T00:00:00Z","timestamp":1788480000000},"content-version":"unspecified","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"abstract":"<jats:p>Introduction: Aromatic L-amino acid decarboxylase is a critical enzyme required for the final step in the synthesis of dopamine and serotonin, two important neurotransmitters. Aromatic L-amino acid decarboxylase (AADC) deficiency is a rare autosomal recessive disorder of neurotransmitter biosynthesis caused by pathogenic variants in the dopa decarboxylase (DDC) gene. An absence or decrease of dopamine and serotonin levels may lead to severe motor and neurodevelopmental impairments. It classically presents within the first 6 months of life with a triad of hypotonia, oculogyric crises and developmental delay. Adult-onset presentations are extremely rare and underreported. Case description: We report the case of a 53-year-old man who presented with progressive left-sided bradykinesia, stiffness, rigidity and resting tremor over a year and a half. Examination demonstrated asymmetrical parkinsonism including facial hypomimia, cogwheel rigidity and a reduced arm swing on the left. A trial of levodopa of up to 1000 mg levodopa equivalent daily dose did not improve his condition. Magnetic resonance imaging of the brain was reported as normal without radiological signs of atypical parkinsonian neurodegenerative disorders. An autoimmune and onconeural antibody panel was negative. The patient\u2019s symptoms progressively deteriorated and he noted dysphagia requiring a tailored feeding plan Dopamine transporter single-photon emission computed tomography was performed demonstrating a marked reduction of nigrostriatal synaptic integrity at the right putamen and modest reduction at the left putamen. Targeted genetic testing identified a homozygous missense variant [NM_000790.3: c.710T&gt;C p. (Phe237Ser)] in the DDC gene, establishing the diagnosis of AADC deficiency. Levodopa was substituted with a direct dopamine agonist (ropinirole) which resulted in a modest clinical improvement; however, dose escalation was limited by nausea. The patient subsequently developed neuropsychiatric symptoms which were managed with mirtazapine and sodium valproate. Conclusion: This case expands the recognised phenotypic spectrum of AADC deficiency and highlights the importance of considering neurotransmitter biosynthesis defects in levodopa-unresponsive adult parkinsonism.<\/jats:p>","DOI":"10.12890\/2026_007317","type":"journal-article","created":{"date-parts":[[2026,9,4]],"date-time":"2026-09-04T09:58:56Z","timestamp":1788515936000},"source":"Crossref","is-referenced-by-count":0,"title":["Adult-onset levodopa-unresponsive parkinsonism as the presenting feature of aromatic l-amino acid decarboxylase deficiency"],"prefix":"10.12890","volume":"13","author":[{"given":"Matthew","family":"Spiteri","sequence":"first","affiliation":[{"name":"Department of Neurosciences, Mater Dei Hospital, Msida, Malta"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Russel","family":"Tilney","sequence":"additional","affiliation":[{"name":"Department of Neurosciences, Mater Dei Hospital, Msida, Malta"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Edith","family":"Said","sequence":"additional","affiliation":[{"name":"Section of Medical Genetics, Department of Pathology, Mater Dei Hospital, Msida, Malta"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Malcolm","family":"Vella","sequence":"additional","affiliation":[{"name":"Department of Neurosciences, Mater Dei Hospital, Msida, Malta"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"10397","published-online":{"date-parts":[[2026,9,4]]},"reference":[{"key":"10.12890\/2026_007317_ref1","unstructured":"Blau N, Pearson TS, Kurian MA, Elsea SH. Aromatic L-Amino Acid Decarboxylase Deficiency. 2023 Oct 12 [updated 2025 Jan 23]. In: Adam MP, Bick S, Mirzaa GM, Pagon RA, Wallace SE, Amemiya A, editors. GeneReviews\u00ae [Internet]. Seattle (WA): University of Washington, Seattle; 1993\u20132026."},{"key":"10.12890\/2026_007317_ref2","doi-asserted-by":"crossref","unstructured":"Bertoldi M. Mammalian Dopa decarboxylase: structure, catalytic activity and inhibition. Arch Biochem Biophys. 2014;546:1-7. doi: 10.1016\/j.abb.2013.12.020.","DOI":"10.1016\/j.abb.2013.12.020"},{"key":"10.12890\/2026_007317_ref3","doi-asserted-by":"crossref","unstructured":"Bisello G, Franchini R, Carmona CAC, Bertoldi M. Mild\/moderate phenotypes in AADC deficiency: Focus on the aromatic amino acid decarboxylase protein. J Inherit Metab Dis. 2025;48(1):e12791. doi: 10.1002\/jimd.12791.","DOI":"10.1002\/jimd.12791"},{"key":"10.12890\/2026_007317_ref4","doi-asserted-by":"crossref","unstructured":"Wassenberg T, Molero-Luis M, Jeltsch K, Hoffmann GF, Assmann B, Blau N, et al. Consensus guideline for the diagnosis and treatment of aromatic l-amino acid decarboxylase (AADC) deficiency. Orphanet J Rare Dis. 2017;12(1):12. doi: 10.1186\/s13023-016-0522-z.","DOI":"10.1186\/s13023-016-0522-z"},{"key":"10.12890\/2026_007317_ref5","doi-asserted-by":"crossref","unstructured":"Leuzzi V, Mastrangelo M, Polizzi A, Artiola C, van Kuilenburg AB, Carducci C, et al. Report of two never treated adult sisters with aromatic L-amino Acid decarboxylase deficiency: a portrait of the natural history of the disease or an expanding phenotype? JIMD Rep. 2015;15:39-45. doi: 10.1007\/8904_2014_295.","DOI":"10.1007\/8904_2014_295"},{"key":"10.12890\/2026_007317_ref6","doi-asserted-by":"crossref","unstructured":"Mastrangelo M, Caputi C, Galosi S, Giannini MT, Leuzzi V. Transdermal rotigotine in the treatment of aromatic L-amino acid decarboxylase deficiency. Mov Disord. 2013;28(4):556\u2013557. doi: 10.1002\/mds.25336.","DOI":"10.1002\/mds.25303"},{"key":"10.12890\/2026_007317_ref7","doi-asserted-by":"crossref","unstructured":"Bisello G, Saris CGJ, Franchini R, Verbeek MM, Willemsen MAAP, Perduca M, et al. An attenuated, adult case of AADC deficiency demonstrated by protein characterization. Mol Genet Metab Rep. 2024;39:101071. doi: 10.1016\/j.ymgmr.2024.101071.","DOI":"10.1016\/j.ymgmr.2024.101071"},{"key":"10.12890\/2026_007317_ref8","doi-asserted-by":"crossref","unstructured":"Himmelreich N, Montioli R, Garbade SF, Kopesky J, Elsea SH, Carducci C, et al. Spectrum of DDC variants causing aromatic l-amino acid decarboxylase (AADC) deficiency and pathogenicity interpretation using ACMG-AMP\/ACGS recommendations. Mol Genet Metab. 2022;137(4):359-381. doi: 10.1016\/j.ymgme.2022.11.003.","DOI":"10.1016\/j.ymgme.2022.11.003"},{"key":"10.12890\/2026_007317_ref9","doi-asserted-by":"crossref","unstructured":"Fusco C, Leuzzi V, Striano P, Battini R, Burlina A; Delphi panel experts\u2019 group; Spagnoli C. Aromatic L-amino Acid Decarboxylase (AADC) deficiency: results from an Italian modified Delphi consensus. Ital J Pediatr. 2021;47(1):13. doi: 10.1186\/s13052-021-00954-4.","DOI":"10.1186\/s13052-021-00954-4"},{"key":"10.12890\/2026_007317_ref10","doi-asserted-by":"crossref","unstructured":"Mckeon A, Vincent A. Autoimmune movement disorders. 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