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Symptoms and impacts on motor function

Symptoms and impacts of aromatic L‑amino acid decarboxylase (AADC) deficiency among individuals with different levels of motor function

Williams K, et al. Orphanet J Rare Dis. 2022.

Publication Date | March 2022
Authors | Williams K, Skrobanski H, Buesch K, Acaster S.
Citation | Orphanet J Rare Dis. 2022;17(1):128.

Aromatic L-amino acid decarboxylase (AADC) deficiency is a rare, autosomal recessive neurometabolic disorder.1 It is primarily associated with a developmental delay, but also presents with a wide range of other symptoms and functional issues, including hypotonia, oculogyric crises (upward deviation of the eyes lasting from seconds to hours), mood and sleep disturbance, autonomic and gastrointestinal dysfunction, and eating difficulties.2–5

Published evidence describing the lived experience of AADC deficiency is limited, making assessments regarding the health-related quality of life (HRQoL) impact of the condition challenging.1 Conventional health technology assessments determine the benefit of interventions using an economic model, which places monetary utility on the impact a particular management approach has on the disease state.1 However, in rare diseases such as AADC deficiency, these sorts of utility estimates may be less useful, due to small sample sizes and the heterogeneity of the disease.1 In addition, the descriptions of these utility assessments don’t always match the lived experiences of patients and caregivers, who play a key role in agreeing on a suitable plan for managing the disease.1

Building on previous work in the area, this study aims to broaden the available qualitative data on what living with AADC deficiency means to patients and their caregivers.1,6 A total of 14 caregivers took part, who were responsible for 13 individuals living with AADC deficiency aged 1–15 years.1 These patients were stratified into 5 health states based on the Peabody Developmental Motor Scales-2 (PDMS-2), which relates to key motor milestones: (1) no motor function, (2) full head control, (3) sitting unsupported, (4) standing/stepping with support, and (5) walking with minimal support (Table 1).1

An interview guide was developed with input from clinical experts and caregivers, to help scrutinise the symptoms and impacts of AADC deficiency.1 Qualitative telephone interviews were conducted with caregivers in Italy, Spain, Portugal, and the United States.1 The interview responses were analysed using thematic analysis, facilitating the comparison of symptoms and impacts across the 5 predefined health states.1

Health stateIndividuals living with AADC deficiency, N (%)
No motor function6 (46.2)
Full head control0 (0)
Sitting unsupported1 (7.7)
Standing/stepping with support1 (7.7)
Walking with minimal support5 (38.5)

Table 1: Health state of study participants living with AADC deficiency (N=13).1


AADC deficiency was reported to have a substantial impact on the day-to-day life of all the affected individuals, regardless of health state.1 Overall, those reported to have better motor function (in particular the ‘walking with minimal support’ group), also reported better functional hand use, communication skills, ability to eat/perform other activities independently, and interactions with their peers.1 Accordingly, those in the ‘no motor function’ and ‘sitting unsupported’ groups experienced very high impairment and were often completely dependent on their caregivers, with caregivers reporting the need to quit or change jobs and having little or no personal time.1

The burden on caregivers was also high across all the health states.1 Those caring for individuals in the ‘walking with minimal support’ group reported being more able to participate in social and leisure activities, although this still required significant forward planning.1 Interestingly, improvements for an individual living with AADC deficiency did not always translate to improvements for the caregiver.1 For example, while feeding oneself was seen as positive for individuals with AADC deficiency, caregivers reported there was an additional time and planning burden vs the use of a feeding tube.1

This study suggests that by developing a greater understanding of the disease experience in each of these AADC deficiency health states, regulators could better assess the beneficial impact of interventions from the patient and caregiver perspective, and more usefully support the decision-making process.1 Furthermore, management approaches which help improve motor function could have the potential to improve other aspects of living with AADC deficiency, for both patients and their caregivers.1


    1. Williams K, et al. Orphanet J Rare Dis. 2022;17:128.
    2. Barow E, et al. Parkinsonism Relat Disord. 2017;36:3–9.
    3. Pearson TS, et al. J Inherit Metab Dis. 2020;43:1121–1130.
    4. Wassenberg T, et al. Orphanet J Rare Dis. 2017;12:12.
    5. Fusco C, et al. Ital J Pediatr. 2021;47:13.
    6. Williams K, et al. Curr Med Res Opin. 2021;37:1353–1361.



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