Adult-Onset Levodopa-Unresponsive Parkinsonism as the Presenting Feature of Aromatic L-Amino Acid Decarboxylase Deficiency.

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 ( 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's 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>C p. (Phe237Ser)] in the 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. LEARNING POINTS: Aromatic L-amino acid decarboxylase (AADC) deficiency, classically an infantile-onset neurometabolic disorder, can present in adulthood as a levodopa-unresponsive parkinsonian syndrome and should be considered in adults with otherwise unexplained atypical parkinsonism.In cases of lack of response to adequate doses of levodopa in an apparent Parkinson's disease phenotype, consideration of a neuroreceptor biosynthesis defect should be made and direct dopamine agonists such as ropinirole can be trailed, as they bypass this metabolic block, and may produce clinical improvement.Unremarkable magnetic resonance imaging does not exclude a neurodegenerative or genetic parkinsonism. Dopamine transporter single-photon emission computed tomography can demonstrate reduced uptake representing nigrostriatal denervation in AADC deficiency. Biallelic dopa decarboxylase molecular genetic testing is first line for diagnosis, guiding drug selection and genetic counselling of the patient and relatives.