Mental health diagnoses in adults with phenylketonuria: a retrospective systematic audit in a large UK single centre

Abstract

Background Recently published European Society for Phenylketonuria (ESPKU) guidelines have recommended a lifelong diet with phenylalanine (Phe) control ≤ 600 μmol/L for phenylketonuria (PKU) patients. This study aimed to identify whether PKU adult patients are at a higher risk of mental health diagnoses if their 2-year average Phe level is higher than the ESPKU European guidelines. Published studies identified by a literature review showed that related studies have been published in American and European PKU study populations but not in the United Kingdom (UK) study populations. Previous studies also involved a smaller number of participants due to this being a rare disease. Results We undertook a retrospective audit at a single large PKU centre in the UK. 244 adult PKU patients at the centre were included, 220 of which had a recorded Phe level. Approximately 75% of the patients in this study did not meet the ESPKU European guidelines for Phe control. A systematic search of the electronic patient record was undertaken looking for mental health diagnoses. Compared to two-year average Phe levels ≤ 600 μmol/L, PKU adult patients with two-year average Phe levels > 600 μmol/L were more likely to have diagnoses of low mood, depression, anxiety, or mood swings, but only low mood reached statistical significance (p < 0.05). Conclusions PKU patients with two-year average Phenylalanine levels greater than ESPKU guidelines may be at greater risk of mental health diagnoses and symptoms. Many of these adult PKU patients will be lost to follow-up, and therefore may be receiving treatment for mental health conditions in the community. Multicentre UK studies and international collaborations are required to overcome low participant numbers in the study of this rare disease.

Expert Consensus on the Long-Term Effectiveness of Medical Nutrition Therapy and Its Impact on the Outcomes of Adults with Phenylketonuria

“…However, opposite conclusions have been published elsewhere [ 39 ] and hence, the safety of treatment targets in PKU will remain a matter of debate until a larger portion of adults with PKU are able to achieve and maintain blood Phe concentrations below at least 600 µmol/L with available treatment options. Despite disagreement on the safety of the upper blood Phe target, it is clear that even in adulthood, blood Phe concentrations above 600 µmol/L are detrimental to mental health outcomes (e.g., anxiety) and executive function, complicating the planning of low-protein meals and impacting the ability to schedule in-clinic appointments, which for some leads to a cycle of suboptimal treatment adherence [ 15 , 26 , 41 , 47 , 48 ]. Statement #7 Consensus Due to the sustainability challenges related to MNT, adults with PKU should be offered pharmacological treatments to lower blood Phe levels when available.…”

“…There is consensus that patients with PKU should avoid elevations in blood Phe throughout life to preserve neurotransmitter production and myelin synthesis [ 1 , 2 , 3 ]. Although the neurotoxic effects of Phe seem to vary between individuals, there is a general trend of increased vulnerability to mental health disorders, including mood disturbances, anxiety and depression, correlated with blood Phe concentrations in adulthood [ 15 , 21 , 42 , 48 , 91 , 92 , 93 , 94 ]. However, in some studies, the relationship between biochemical markers and neuropsychological symptoms was not significant [ 95 , 96 , 97 ].…”

Phenylketonuria from the perspectives of patients in Türkiye

“…It has been reported that mood alterations, such as anxiety and depression, are more prevalent in PKU patients, particularly in those with higher phenylalanine concentrations than recommended [ 10 , 23 ]. In the present study, angry/irritable mood was the most frequent unfavorable symptom reported in all age groups, followed in the order of frequency by failure to concentrate/difficulty in focusing and sad mood in pediatric group; failure to concentrate/difficulty in focusing and difficulty in understanding the subjects in the class/at work/daily life in the adolescent group; feeling of tiredness and failure to concentrate/difficulty in focusing in the adult group.…”

Adult PKU Clinics in the UK—Users’ Experiences and Perspectives

“…In a review of 39 articles, neurological signs and symptoms were present in adults who were early diagnosed and treated, particularly if they discontinued treatment after childhood [25]. Adults may also have impairments of reasoning, visual-spatial attention, processing speed, sustained attention, visuo-motor control, inhibitory control, working memory and cognitive flexibility [22,26,27] and increased risk of emotional and behaviour deficits (e.g., attention deficit, hyperactivity, depression, anxiety, low mood, mood swings, poor self-image, withdrawal, and a lack of autonomy and drive) [23,28,29]. Psychiatric symptoms such as panic disorders and agoraphobia are reported [30].…”

“…European and American guidelines on the management of PKU recommend maintenance of blood Phe levels in the therapeutic target range of: Europe: 120-360 µmol/L in patients <12 years of age and 120-600 µmol/L in patients ≥12 years; USA: 120-360 µmol/L in all age groups [5,35]. However, blood Phe control deteriorates with age, and most adult patients cannot maintain blood Phe control within target ranges (i.e., blood Phe levels exceeding 600 µmol/L) [29,[36][37][38][39]. Some adults may partially follow dietary treatment, commonly without a Phe-free/low-Phe protein substitute.…”