Living with a UCD can be extremely debilitating depending on the severity of the condition. Intense pharmacological treatment, coupled with strict dietary control, means that both carers and children living with UCD are in a constant state of monitoring. Whilst HrQoL has previously been investigated primarily through survey studies, which can be limited in exploring experiences in-depth within context [27, 28, 30], this study successfully explored the burden of pharmacological treatment and subsequent impact on HrQoL in children living with UCD and their carers. After completing semi-structured interviews with carers of nine children living with UCD who had successfully transitioned from one medication to another, themes concerning psychological health, physical health and social participation emerged. Mainly positive aspects were described by carers in relation to the transition from either NaPBA or NaBZ to GPB when considering HrQoL. One negative element emerged regarding the specific syringes needed to administer GPB and experiencing difficulties acquiring them. This induced a level of stress in carers trying to manage their child’s ammonia levels. Children and carers were affected simultaneously in a variety of ways during pharmacological treatment and transition, demonstrating the burden placed on both the child and the individual administering medication, typically the carer.
The psychological impact of managing a UCD through pharmacological intervention, drawing from the lived experience of carers, was exceptionally high. Administration emerged as one of the main psychologically challenging aspects of pharmacological management. Linked implicitly to the negative attributes attributed to UCD treatments [19], adhering to a strict administration regime placed significant psychological strain on carers. One account described the act of having to physically restrain their child whilst taking NaBZ to ensure that the medication was taken as prescribed. For many, the most challenging aspect of pharmacological management was the administration of the drug. Previous research has illustrated how negative attributes of a drug can be significant barriers to adherence in patients with inborn errors of metabolism, such as the taste of the medication, the frequency of administration and associated side effects [14]. The problems associated with medication in the current study population (tolerability, dosage, nausea and smell), and the child’s general reluctance to take their medication, were often attributed to elements such as poor taste, burden of treatment and subsequent nausea experienced after the medication had been administered. The “battle” that many carers used metaphorically induced a deep sense of worry, whilst children experienced trepidation at administration times. It is important to note that the administration “battle” was alleviated somewhat after the transition onto GPB. In line with research describing the more positive elements of GPB [19], relying on GPB as primary pharmacological treatment could provide some respite for carers.
Negative emotions were frequently described and alluded to by carers, illustrating the multifaceted nature of the condition and pharmacological regime. Fear was an emotion both encountered and experienced by carers. Given the rigorous pharmacological management regime that is adhered to, many acquaintances, friends and family were scared to take full responsibility for the child living with UCD through fear of mismanaging the condition. The psychological and pragmatic burden of this was substantial, with carers shouldering the entirety of care responsibilities. Coupled with this were feelings of loneliness owing to the rarity of the condition and misunderstanding from others, as well as inordinate amounts of worry, especially when children experienced side effects that impacted upon subsequent administration times and doses.
The primary aim of pharmacological management in UCD is to maintain stable ammonia levels, thus preventing potential complications such as hyperammonemic episodes. The struggle to maintain safe ammonia levels was described in great detail by carers. Carers remarked how, on the initial treatment prior to the transition to GPB, ammonia levels were higher and would fluctuate more frequently. The impact of elevated ammonia levels in children living with UCD culminated into frequent hospitalisation and added burden for both child and carer. A number of participants noted that their child’s ammonia levels had reduced and become more stable following their transition onto GPB. This mirrors research suggesting that ammonia levels are significantly lower on GPB as compared to NaPBA, with reduced instances of abnormal values [38]. The consequential effect of improved ammonia levels for children living with UCD meant reduced hospital visits and alleviated worry for the carer. Again, it could be suggested that relying primarily on GPB as the main mode of pharmacological management reduces burden on both children and carers by reducing engagement with tertiary care and a reduction in negative emotions experienced, such as worry.
The effect of pharmacological management manifested itself in severe impacts on social participation including school, family events and holidays. Families described how difficult managing relationships with the child’s school was, as some schools failed to fully understand the severity of the condition. Whilst providing schools with a day-to-day management plan is recommended [3] and was commonly reported by carers, their experiences suggested that knowledge underpinning pharmacological treatment for UCD in teachers and school staff was missing. The rigorous nature of the day-to-day plan, above and beyond teacher’s daily routine, seemed to cause major inconvenience which ultimately impacted upon the child living with UCD and their wellbeing. Moreover, carers had experienced instances where their child was unable to participate in extracurricular school activities, or even mainstream education despite carers feeling that this would benefit their child socially. This mirrors previous research where parents of UCD patients possessed great concern over the social challenges their child faced [35]. The disparity between schools and carers is evident, suggesting that further work should seek to bridge the gap between education providers and the UCD community to better support children both in their education and in their social wellbeing.
Considering the impact of pharmacological management on carers involved in administering UCD medication, HrQoL should be a core consideration alongside reducing the child’s ammonia levels. These findings suggest that GPB reduces carergiver’s stress due to improved characteristics relating to taste, frequency and administration method. Further research is required to fully understand how the transition to GPB alleviates negative affect for the caregiver as well as the child living with UCD. The results of this work will facilitate future work that could provide both practical and emotional support to families living with UCD. Findings suggest that transitioning to GPB could alleviate some pragmatic challenges faced by families but, ultimately, that battling the condition will persist throughout the child’s life. It is vital that pharmaceutical companies and decision makers, including clinicians, ensure that enough syringes are produced and made readily available to reduce anxiety for carers. Greater attention should be placed on providing families and carers specifically with specialist resources to cope with the daily challenges that the condition presents, such as emotional support and respite. Medical professionals should consider GPB as the most appropriate option when considering carer’s HrQoL but also, based upon the carer perspective, the child’s experience of taking medication for their condition. Improved taste, timing and administration of GPB appears to contribute towards greater medication adherence. Consequently, this should help manage ammonia levels in a more consistent way, which is key to reducing the risk of hyperammonemic episodes, further developmental damage and the negative impact this may have on quality of life.
There are limitations to this study. Four participants were relatively early in their transition from previous treatments to GPB (within 6 months), meaning that they may not have had extensive experience in discussing long-term effects of GPB on HrQoL as opposed to previous treatments. Given GPB is a relatively new treatment option in terms of accessibility, determining the long-term impact of GPB on HrQoL may only be attainable in time when more UCD patients are engaged with GPB as their primary treatment option. Coupled with this, participants were primarily interviewed during the summer months during school holidays. One child had yet to begin formal schooling. Understanding the full range of schooling challenges is imperative to improving the apparent misunderstanding that carers’ encounter on a regular basis.
The sample of participants in this study cared for UCD children who were primarily of school age. Evidence suggests that mortality rates in neonatal patients is fairly high compared to healthy counterparts [39] suggesting that a significant number of UCD patients do not survive through their early years without strict pharmacological management. Whilst life expectancy has yet to be assessed in times where greater treatment options are available, future research should attempt to recruit older UCD patients to understand HrQoL in later stages of life and for those who may be living in a more independent fashion. Similarly, experiences of living with UCD could be different between the different types of metabolic deficiency, such as between ornithine transcarbamylase (OTC), carbamoyl phosphate synthetase 1 (CPS1) and argininosuccinate synthetase (ASS). Stratifying the severity and type of condition could elucidate any specific challenges that may exist between conditions and mode of drug intake. Further research could also investigate how stress-reducing interventions are received by carers of children with UCD and their impact on stress levels.