Aromatic L-amino acid decarboxylase deficiency: a systematic review

Aim: To gain greater knowledge regarding the natural history of aromatic L-amino acid decarboxylase (AADC) deficiency, a genetic disorder that causes severe deficits in motor and cognitive development. Materials & methods: A systematic literature review was performed of all case reports and clinical studies published through December 2019 of patients with AADC deficiency. The data were summarized descriptively. Results: The search identified 94 publications that described 237 unique patients. Mean (standard deviation) age at diagnosis was 3.2 (+/- 5.7) years and 16 deaths were reported. Most patients (57%) received the standard of care therapies, which showed limited efficacy in this patient population. Conclusion: AADC deficiency is a devastating disease and prospectively defined natural history studies are warranted to further understand this disease. Plain language summary: What is this article about?: The article describes an analysis of the published medical literature that summarized the characteristics of patients with aromatic L-amino acid decarboxylase (AADC) deficiency. AADC deficiency is a very rare genetic disorder that results in loss of AADC enzyme activity and consequently the lack of the neurotransmitters dopamine and serotonin resulting in patients having severe loss of muscle and cognitive function. Data from publications were used to evaluate the frequency of specific symptoms of the disease, muscle function, underlying genotypes and therapies used to treat AADC deficiency. What were the results?: The results show that AADC deficiency is present worldwide and is due to a variety of underlying genetic mutations in the gene that produces the AADC protein. Diagnosis of the disease is often delayed and does not usually occur until about 3 years of age. Often, these patients die within the first decade of life. The standard treatment of AADC, which does not involve gene therapy, is limited in its ability to treat the symptoms of the disease with only about 3% of patients, who at most have head control by 2 years of age, improving following treatment. What do the results of the study mean?: This study clearly indicates that AADC deficiency is a devastating disease in which standard therapy is not effective and highlights the need for new therapies, including gene therapies, that treat the primary cause of the disease.