Burden of illness in aromatic l-amino acid decarboxylase deficiency.

Objectives: Deficiency of aromatic l-amino acid decarboxylase (AADC), a key enzyme in monoamine synthesis, is an ultrarare disorder of monoamine synthesis estimated to affect fewer than 50 patients in the United States, although rates of misdiagnosis may be high. In its severe form, this congenital hypodopaminergic state results in profound hypotonia, developmental impairment, oculogyric crises, dystonia, dysautonomia, hypoglycemia, and premature death. The present study assesses the burden of illness for patients and caregivers by assessment of medical resource utilization (MRU) and quality of life (QOL) measures to enable future health technology assessment activities for emerging therapeutic options. Methods: Data from patients' medical records from the prior two years were examined to estimate burden in terms of direct costs; indirect care burden (including caregiver impact on sleep, health, and vocational opportunities) and QOL were also assessed using the BURQOL-RD, AQoL-6, and Visual Analogue Scale questionnaires. Results: Data were available for five US cases (three males, two females; age, 2-24 years, median, 5 years). MRU ranged from $6162.73 to $49 043.94 annually per patient. Although the proportion of costs (inpatient and outpatient visits, labs/tests, drugs, devices/durable medical equipment, and speech/physical therapy) varied greatly, the average annual direct cost of healthcare was approximately $25 000. Caregivers described profound care burden and QOL effects, with an average indirect care burden cost assessment of nearly $43 000 yearly. The mean economic burden of AADC deficiency per year was estimated at $68 000. Conclusion: MRU and QOL varied considerably by patient. This is attributable to the disease's variable phenotypic severity and differing patient needs. Frequent contact with the healthcare system, however, is a constant for patients with AADC deficiency and their caregivers. Quantifying MRU and QOL for rare genetic diseases is critical for assessing the value of emerging targeted therapies.