OBJECTIVES: Aromatic L-Amino acid Decarboxylase (AADC) deficiency is a rare disorder of monoamine synthesis. A few hundred cases have been reported globally with a varied phenotypic severity. There is a limited understanding of the clinical course and burden of AADC deficiency. This literature review and case report data analysis aimed to determine the timing of the onset and frequency of clinical signs and symptoms in patients with AADC deficiency.

METHODS: A systematic literature search was conducted identifying all case reports of series of patients with AADC deficiency who reported the age at onset of clinical signs and symptoms. Demographics and clinical data were extracted, categorized (developmental delays, movement disorders, tone regulation, autonomic function problems, cardiovascular/gastrointestinal/endocrine/respiratory problems and others), and classified by age of onset of clinical signs and symptoms.

RESULTS: From the 29 studies that met the inclusion criteria, 66 (50% male) AADC deficient patients, with mean age at diagnosis of 4,4 years (SD 5,3 years; 23 % missing data), were included in the analysis. For 29% of the patients, the first clinical signs/symptoms were reported as early as during the first 30 days after birth. By the age of 2 years, 94% of patients had experienced at least 1 of the clinical signs and symptoms/events of the disease; with 13% and 28% having experienced the 6 main signs/symptoms by 2 years and 6 years of age, respectively. Over the observation period, all patients experienced ≥1 sign or symptom deemed to contribute to the burden of AADC deficiency; movement disorders (98%), tone regulation (94%), developmental delays (83%), and autonomic dysfunction (77%) were most frequently reported.

CONCLUSIONS: AADC deficiency is associated with a high disease burden, regardless of age of onset of clinical symptoms. The accumulation of the disease burden across lifetime reflects the progression of the disease.