Objective: We review the presentation of a 3-month-old patient who came to our institution with symptoms of dystonia, oculogyric crises, hypotonia, developmental delay, and dysphagia, diagnosed with AADC deficiency based on whole exome sequencing results, in the interest of adding to the sparse number of currently documented cases, and to provide a review of the relevant literature.

Background: Childhood dystonias are relatively common disorders with heterogenous mechanisms underpinning presentations creating diagnostic challenges. AADCD is an early onset, rare, autosomal recessive neurometabolic disorder that leads to a severe combined deficiency of serotonin, dopamine, norepinephrine, and epinephrine. The key clinical symptoms are hypotonia, movement disorders (oculogyric crisis, dystonia, and hypokinesia), developmental delay, and autonomic symptoms. First line treatment includes dopamine agonists, pyridoxine, MAO inhibitors

Method: Informed consent was obtained from the patient’s family for sharing of both historical and videographic information.

Results: Our patient presented initially with posturing spells of his bilateral upper extremities with internal rotation, elbow extension, and wrist flexion, with hyperkinetic dystonia distally, which started around age 2 months. Spells progressed to include neck extension and upward gaze deviation without loss of consciousness. Initially symptoms were episodic (no symptoms between the episodes) and they progressed to constant movements. There was improvement initially with levodopa trial (3mg/kg/day) but the effect did not sustain. Initial workup included MRI brain and video EEG which were negative. Given the high suspicion for dopamine synthesis defects (oculogyric crisis, some response to levodopa), genetic testing was recommended. It revealed mutation in DDC gene (c.1234C>T (p. Arg412Trp) and c.367G>A(p.Gly123Arg)). Patient is currently being evaluated for a clinical trial for gene therapy.

Conclusion: AADC deficiency has significant neuromuscular implications that severely impact patients’ day to day lives with diagnosis and treatment being challenging. The disease presents similar to other disease courses upon initial presentation, resulting in difficulty of diagnosis. This patient with AADCD, adds to the limited but growing body of reports currently available and highlights the need for further research and understanding of the disease and treatments

References: Manegold, C., Hoffmann, G. F., Degen, I., Ikonomidou, H., Knust, A., Laass, M. W., Pritsch, M., Wilichowski, E., & Hörster, F. (2009). Aromatic L-amino acid decarboxylase deficiency: clinical features, drug therapy and follow-up. Journal of inherited metabolic disease, 32(3), 371–380. https://doi.org/10.1007/s10545-009-1076-1

Pons, R., Ford, B., Chiriboga, C. A., Clayton, P. T., Hinton, V., Hyland, K., Sharma, R., & De Vivo, D. C. (2004). Aromatic L-amino acid decarboxylase deficiency: clinical features, treatment, and prognosis. Neurology, 62(7), 1058–1065. https://doi.org/10.1212/wnl.62.7.1058

Tay, S. K., Poh, K. S., Hyland, K., Pang, Y. W., Ong, H. T., Low, P. S., & Goh, D. L. (2007). Unusually mild phenotype of AADC deficiency in 2 siblings. Molecular genetics and metabolism, 91(4), 374–378. https://doi.org/10.1016/j.ymgme.2007.04.006

Wassenberg, Tessa, et al. “Consensus guideline for the diagnosis and treatment of aromatic l-amino acid decarboxylase (AADC) deficiency.” Orphanet journal of rare diseases 12.1 (2017): 1-21.

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MDS Abstracts - https://www.mdsabstracts.org/abstract/aromatic-l-amino-acid-decarboxylase-deficiency-a-rare-disease-case-report-and-literature-review/