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

BackgroundUrea 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).ResultsTwenty-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 pound million with unlicensed specials accounting for 3 pound 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.ConclusionsTo standardise the treatment of UCDs within and between metabolic centres in the UK, there is merit in developing a UK-specific treatment guideline.