Perspectives on long-term medical management of urea cycle disorders: insights from a survey of UK healthcare professionals

Abstract

Background: Urea cycle disorders (UCDs) are rare inborn errors of metabolism which impact the body's ability to detoxify ammonia produced during protein metabolism. In the UK, there is a nationally adopted guideline for the emergency management of hyperammonaemia in UCD patients, however there is no guideline for long‑term management, and treatment decisions are left to the discretion of individual healthcare professionals (HCPs).

Results: Twenty-three HCPs, comprising 13 (57%) metabolic consultants, two (9%) specialist nurses, four (17%) pharmacists, and four (17%) dietitians, participated in interviews to document their attitudes and beliefs regarding the long‑term management of UCD patients, including their current practices, treatment goals, and clinical ambitions. The highest priority for 14/23 (61%) of HCPs was to minimise the risk of hyperammonaemia, however the ammonia level that HCPs advised they aimed for varied significantly, with some targeting above the upper limit of normal. Glycerol phenylbutyrate was the highest ranked ammonia scavenger treatment amongst HCPs for safety, tolerability, duration of scavenging action and reducing patient burden, and HCPs suggested that it would be the first-line treatment in an updated guideline. All prescribing HCPs agreed they would prefer their patients receive a licenced product rather than an unlicensed one for reasons including more reliable supply, greater insurance/legitimacy, and the reassurance of regulatory scrutiny and approval. However, analysis of NHS England's dispensing data between July 2023 and June 2024 indicated annual spend on nitrogen scavengers of £6.7 million with unlicensed specials accounting for £3 million (45%) of the total. Differences between HCPs in the awareness of clinically relevant characteristics of ammonia scavengers, including their sodium and propylene glycol content, were observed.

Conclusions: To standardise the treatment of UCDs within and between metabolic centres in the UK, there is merit in developing a UK-specific treatment guideline.

Keywords: Evidence-based practice; Hyperammonaemia; Nitrogen scavengers; UCD survey; UCD treatment; Urea cycle disorders.

Fig. 1

Demographics of the HCPs that took part in the survey. The HCPs represented four different roles involved in the treatment of patients with urea cycle disorders. Participants were involved in the treatment of adult patients, paediatric patients, or both

Fig. 2

Additional demographics of participants. Bars show median value. The HCPs who participated in the survey had a median of 12 years in practice and were involved in the care of a median of 31 patients with UCDs

Fig. 3

Differences between the available nitrogen scavengers in terms of their patient-relevant attributes. Participants were asked to rank the available scavengers based on what was best for the patient. The number of times each drug ranked as best for patient (ranked as number 1, i.e. best for patient) is shown above the bar. GPB liquid (green) was ranked as best for patient across all attributes. NaBz– sodium benzoate, NaPBA– sodium phenylbutyrate, GPB– glycerol phenylbutyrate

Fig. 4

Use of nitrogen scavengers. HCPs indicated that currently, the majority of their patients were prescribed NaBz (blue, 45%). However, if they were to be presented with 100 new UCD patients (future use), the majority of their patients would be on GPB (80%). Bars show median number of patients. NaBz– sodium benzoate, NaPBA– sodium phenylbutyrate, GPB– glycerol phenylbutyrate

Fig. 5

Satisfaction with the level of disease control that can be achieved in UCD patients on different nitrogen scavengers. The number of respondents varied as HCPs were only able to answer based on the scavengers they use in their practice

Fig. 6

Indication as to what extent the presence of each of the following attributes reflects the potential failure of UCD disease management (n = 22). Outcomes are displayed in order, with the attributes that are the strongest indicator of treatment failure at the top of the chart, and attributes that were most often considered to not be an indicator of treatment failure at the bottom

Fig. 7

How often certain outcomes are achieved by HCPs in their UCD patients (n = 21). Outcomes are displayed in order, with the outcomes almost always achieved at the top of the chart, and outcomes that were indicated to most frequently never be achieved at the bottom