Abstract
Rationale
Phenylketonuria (PKU) is a metabolic condition that requires treatment for life. There is increasing evidence that chronic illnesses put strain on relationships and marriages. However, no studies have examined the unique factors that metabolic conditions have on affected individuals and their relationship satisfaction. We surveyed a population of adult patients with PKU and assessed how management, treatment, and lifestyle factors impact their relationship satisfaction.
Purpose
The purpose of our study was to explore whether factors such as involvement of partner in PKU management, impact of challenges unique to PKU (e.g., diet, family planning, mood disturbances), and PKU treatment types were associated with the degree of relationship satisfaction.
Method
We surveyed adult patients with PKU (n = 82) who were either currently in or had previously been in a long-term relationship. We developed a 78-question survey that included unique questions regarding lifestyle, treatment, and management of their PKU in addition to a validated Relationship Assessment Score. Questions included single choice, multiple choice, and 3 open-ended questions.
Results
We found that higher relationship satisfaction was associated with increased partner involvement, increased health, and adherence to recommended PKU treatments. Participants utilizing both diet and pharmaceutical treatment had the highest relationship satisfaction. Finally, participants who reported that their PKU did not contribute to the ending of a previous relationship reported higher relationship satisfaction scores.
Conclusion
This study suggests that involvement of partners in the management and treatment of a chronic illness and adherence to recommended treatments can significantly improve relationship satisfaction.
Supplementary Information
The online version contains supplementary material available at 10.1007/s12687-023-00667-7.
Introduction
Phenylketonuria (PKU, OMIM #261600) is an inborn error of metabolism. Individuals with PKU do not have normal function of the enzyme phenylalanine hydroxylase to break down phenylalanine, which is present in protein. Phenylalanine builds up in the brain as a result, causing neurologic damage. There is no cure for PKU. Management involves lifetime treatment with a strict low natural protein diet, medical food with minimal or no levels of phenylalanine, and/or medications. Recommended surveillance for adults involves monthly blood level checks with the goal to keep phenylalanine levels in the range of 120–360 µmol/l (Vockley et al. 2014).
Adherence to this diet and cost for PKU treatment can be extremely difficult, expensive, and time-consuming (Rose et al. 2019), and many individuals struggle with this strict dietary management. There are currently two medications approved by the FDA for treatment of PKU: sapropterin dihydrochloride (Kuvan®, BioMarin Pharmaceuticals Inc., Novato, CA) and pegvaliase (Palynziq®, BioMarin Pharmaceuticals Inc., Novato, CA). Additionally, clinical trials for new medications and gene therapy are ongoing. These new treatments offer non-diet–based options for controlling phenylalanine levels and thus can offer greater ease of compliance and more successful long-term management of PKU; however, they have been reported to be the greatest expense toward PKU management overall (Rose et al. 2019). The goal of both diet and medications is to keep phenylalanine levels low as well as to improve neuropsychological outcomes.
High phenylalanine levels can lead to neuropsychiatric problems and neurocognitive deficits (anxiety, headaches, mood changes), and issues with information processing, and memory impairment in adults (Gentile et al. 2010; ten Hoedt et al. 2011). Long-term elevation of Phe levels can cause developmental delay and intellectual disability. Frequently, patients state that the diet is unpalatable and socially isolating (Ford et al. 2018; Zurflüh et al. 2008). This can lead to individuals not staying compliant with treatment or having difficulty forming and keeping stable social relationships (Simon et al. 2008). When off-diet, quality of life can remain low, with patients experiencing severe emotional distress (Bik-Multanowski et al. 2008; Rose et al. 2019). However, other studies have shown that with proper treatment and management individuals with PKU have no statistical differences in quality of life compared to control populations (Aitkenhead et al. 2021; Bosch et al. 2007; Vieira et al. 2017). MacDonald et al. (2010) reported that common barriers to dietary compliance include low family cohesion (such as the impact of divorce) and poor social and/or family support.
There is increasing evidence that comorbid conditions such as poor physical and mental health with chronic illness can put stress on marriages or relationship satisfaction (Downward et al. 2022; Joung et al. 1998; Milrad et al. 2019; Wilson and Waddoups 2002), with a common concern involving finances (Estecha Querol et al. 2020). A partner’s illness may require spousal caregiving, which can add to the emotional and psychological stress (Pinquart and Sörensen 2011). Conversely, couples with higher concordance in health and health behavior tend to have greater relationship satisfaction (Baucom et al. 2020; Røsand et al. 2012). In type 2 diabetes for example, greater satisfaction with partners and partnership support is related to better physical health (Robles et al. 2014) and is associated with better adherence to treatments (Stephens et al. 2013).
Within the PKU community, adults who receive support from their partners and family reportedly cope better with dietary treatment (Ipsiroglu et al. 2005). Although one study of patients with PKU found that 31% of respondents said that their relationship with their partner was affected due to difficulties surrounding their diagnosis (Ford et al. 2018), no research has examined which specific factors of PKU impact a patient’s partnership satisfaction. Identifying these factors is essential to providing patient-specific support and care. This current study surveyed patients with PKU to explore whether factors such as partnership support or challenges unique to PKU (e.g., diet, family planning) were associated with the degree of their relationship satisfaction. Our hypothesis was that participants who reported better PKU management and adherence to treatment will also report higher relationship satisfaction.
Materials and methods
Participants
Adults with PKU were invited to participate. To be eligible, participants must have been diagnosed with PKU, be at least 23 years of age, currently or previously been in a relationship for a minimum of 6 months, and live/lived with their partner. This age minimum was derived from Lantagne and Furman, (2017) which showed that long-term relationships become far more common in early adulthood and are shown to be just as supportive as those in adulthood beginning at age 23. By setting the age cutoff at 23 years, participants could still report on long-term relationships occurring within the past 5 years (up to age 18). This ensured respondents had the option to report on a preceding long-term relationship if a more recent one had not transpired. The survey collected information on their most recent (or current) relationship.
Recruitment
PKU support groups based online (PKU World Group, Everything PKU, and PKU Alliance and Support Group), the National PKU Alliance (NPKUA), and the Metabolism Clinic at Indiana University Health were involved in the survey distribution. Recruitment methods included distribution of flyers and contacting patients via the Metabolism Clinic at Indiana University Health. The NPKUA recruited by sending a targeted eBlast, including the survey in their Registry Newsletter, and posting on their social media accounts on Facebook, LinkedIn, and Instagram that reached an estimated 15,000 adults with PKU.
All participants consented to participate. At completion of the survey, participants had the option to provide their email address for a chance to win one of ten $25 Amazon gift cards. The survey was open from June 20 to August 30, 2022. The study, including recruitment materials, was approved by the Indiana University Institutional Review Board (Protocol # 14404).
Instrumentation
Data were collected and managed using REDCap (Research Electronic Data Capture) electronic data capture tools hosted at Indiana University (Harris et al. 2009, 2019). REDCap is a secure, Web-based software platform designed to support data capture for research studies. The survey comprised 78 questions including single-choice, multiple-choice, and 3 open-ended questions.
Demographic information included participant age, gender, race, ethnicity, level of education, employment, income, number of children, and rating of their health (poor, fair, good). Similar demographics (reported by the participant) were collected for the partner. The survey consisted of questions on several aspects of PKU: dietary management, medication treatments, lifestyle factors, side effects of PKU, involvement of partner, straining factors of PKU, and the validated Relationship Assessment Scale (Hendrick 1988).
Relationship satisfaction
The Relationship Assessment Scale consisted of 7 items (e.g., “in general, how satisfied are you with your relationship?”) answered on a 5-point Likert scale ranging from 1 (low satisfaction) to 5 (high satisfaction), with no text. The relationship assessment score (RAS) for each respondent was calculated by adding the 7-item scale values, with reverse-scoring for questions 4 and 7, resulting in a score that ranged from 7 to 35. This scale was validated on a sample of college students and college couples, and successfully predicted stability of the relationship measured by the couples staying together vs breaking up (Hendrick 1988; Hendrick et al. 1998).
Treatment and management of PKU
Participants were asked about the most recent treatment recommendations made by their care team and what treatments they are currently following. Based on these responses, individuals were assigned to two groups: those currently following all recommended treatment and those following one but not all recommended treatments. Participants who had been prescribed treatments but were not currently following them were coded as none. Participants were further organized into treatment categories based on self-reported treatments being followed: diet alone (restricted natural protein diet and medical food (protein substitute), or both), pharmaceuticals alone (pegvaliase (Palynziq®) or sapropterin dihydrochloride (Kuvan®)), or both (restricted natural protein diet and/or medical food with a pharmaceutical), or none.
Frequency of participant phenylalanine level checks was collected (weekly, more than once a month, once a month, 3–4 times year, once a year, and less than once a year, Supplemental Table 1). Responses were collapsed to create two groups: those who checked their levels at least once a month, and those who checked less than once a month. Participants were also asked their last phenylalanine level < 120 µmol/L (< 2 mg/dL), 120–359.9 µmol/L (2–5.99 mg/dL), 360–599.9 µmol/L (6–9.99 mg/dL), 600–1199.9 µmol/L (10–19.99 mg/dL), > 1200 µmol/L (20 mg/dL), and I do not remember; Supplemental Table 2). Responses were collapsed following ACMG treatment guidelines (Vockley et al. 2014) to those who selected < 360 µmol/L (6 mg/dL) and ≥ 360 µmol/L (6 mg/dL), with “I do not remember” combined into the ≥ 360 µmol/L (≥ 6 mg/dL) group.
Lifestyle factors surrounding PKU
Participants were asked to select up to 8 unique factors of PKU (check all that apply) that have strained their relationship, e.g., finances or eating out, including the option of “nothing has strained the relationship” (all options are provided in Supplemental Table 3 Online Resource 1). For each factor selected, the participant was asked how significantly that factor impacted their relationship, with Likert responses of 1 = severely, 2 = somewhat, and 3 = slightly. The Likert responses were summed, and the average score based on the number of factors selected by each individual was calculated, with lower scores indicating a more severe impact. The average severity of impact for each individual straining factor was also calculated. In a separate question, participants were asked “Did your PKU contribute to any issues that resulted in the ending of any previous long-term relationship” with answer options being “a lot, a little, or none.”
How involved a partner was in management of their PKU was asked (very involved, moderately involved, and not involved) and the extent of partner assistance with things like mixing formula (i.e., medical food) or preparing meals was assessed by asking about 7 unique actions (select all that apply), provided in Supplemental Table 4 (Online Resource 1). Participants were also asked to select up to 8 potential factors of PKU that the participant and their partner have disagreed about (check all that apply), e.g., adherence to treatment and family planning, with the option of “none” (all options provided in Supplemental Table 5, Online Resource 1).
Lastly, three supplemental open-ended questions were explored and were not factored into analysis. The questions asked were “please further comment about your above health needs and any difficulties you experience (number responses = 43),” “please further comment on if you believe your PKU diagnosis has impacted any of your relationships (both negatively and positively) (number responses = 37),” and “is there anything else you would like to add about your partner and how their health may have impacted your relationship? (number responses = 23).” All responses are in Supplemental Table 6, Online Resource 1.
Statistical analysis
To explore factors associated with RAS, we first evaluated if the following variables were individually predictive or associated with RAS: demographics: age (participant and partner), income, education, current relationship status (single, divorced, or separated); current relationship (in a relationship/married/domestic partnership vs previous relationship), factors describing PKU management (partner involvement, partner disagreements, frequency of phenylalanine checks, last phenylalanine level, and if PKU contributed to issues or the ending of a previous relationship, treatment type, and impact and severity of PKU specific strains). Quantitative variables were evaluated using Pearson correlation, categorical variables with two groups were assessed with a t-test, and an analysis of variance (ANOVA) was used for categorical variables with three or more groups. Factors with p < 0.05 were included in an automated stepwise selection regression model to account for all variables. As this study was specifically designed to explore how PKU management affected relationship satisfaction, frequency of Phe level checks and the last Phe level were included in the stepwise model if p < 0.10. The automatically selected variables (p < 0.05) were entered into one final ANOVA model to evaluate the contribution of each factor after accounting for all selected factors identified by the stepwise selection process. Results from the type 2 sum of squares are reported, as these p-values represent prediction of RAS due to the factor after adjusting for all other variables in the model. Adjusted means and standard errors (SE) are reported, and Bonferroni-corrected p-values for post hoc pairwise comparisons of significant (p < 0.05) categorical variables are provided. Comparisons of categorical variables were evaluated using a Fisher’s exact test. SAS version 9.4 was utilized in all analyses.
Results
Recruitment
There were 19 completed responses to the survey out of an estimated 90 eligible participants recruited through Indiana University Metabolic Genetics Clinic for response rate of 21.1%. Recruitment through the NPKUA and online social media groups provided 36 and 26 responses respectively, with a response rate < 1%. One participant did not note recruitment source. There were 111 total responses to the survey. Of these responses, 6 were ineligible as they did not meet recruitment criteria and 23 did not complete required survey questions. This resulted in a total of 82 eligible participants whose characteristics are summarized in Table 1.
Table 1.
Participant and partner demographics (n = 82)
| Respondent demographics | Percent (n) | |
|---|---|---|
| Participant | Partner | |
| Gender | ||
| Female | 72.0 (59) | 28.0 (23) |
| Male | 26.8 (22) | 70.7 (58) |
| Non-binary | 1.2 (1) | – |
| Transgender female | – | 1.2 (1) |
| Age (mean (range)) | 37 (23–72) | 37 (23–73) |
| Relationship status | ||
| Current | n = 70 | |
| In a relationship | 19.5 (16) | – |
| Married or domestic partnership | 65.9 (54) | – |
| Previous | n = 12 | |
| Single | 8.5 (7) | |
| Separated | 2.4 (2) | – |
| Divorced | 3.7 (3) | |
| Length of relationship | ||
| 6 months – 1 year | 4.9 (4) | – |
| 1 ± 2 years | 7.3 (6) | – |
| 2 ± 3 years | 9.8 (8) | – |
| 3 + years | 78.0 (64) | – |
| Education | ||
| Less than high school | – | 3.7 (3) |
| High school | 8.5 (7) | 14.6 (12) |
| Some college | 24.4 (20) | 13.4 (11) |
| Associate degree | 12.2 (10) | 18.3 (15) |
| Bachelor’s degree | 36.6 (30) | 37.8 (31) |
| Post-graduate degree | 18.3 (15) | 12.2 (10) |
| Income | n = 81 | |
| < $68,000 | 42.0 (34) | – |
| > $68,000 | 58.0 (47) | – |
| Race | ||
| Asian | 2.4 (2) | – |
| Middle Eastern of North African | 1.2 (1) | – |
| White | 96.3 (79) | – |
| Employment | ||
| Full-time | 65.9 (54) | 78.0 (64) |
| Part-time | 17.1 (14) | 11.0 (9) |
| Unemployed | 6.1 (5) | 4.9 (4) |
| Student | 3.7 (3) | 3.7 (3) |
| Unable to work | 7.3 (6) | 2.4 (2) |
| Health/partner health | n = 81 | |
| Poor | 6.1 (5) | 6.2 (5) |
| Fair | 31.7 (26) | 39.5 (32) |
| Good | 62.2 (51) | 54.3 (44) |
| PKU management | ||
| Poor | 9.8 (8) | – |
| Moderately | 45.1 (37) | – |
| Fairly well | 45.1 (37) | – |
| Treatment/s following | ||
| Diet only | 34.1 (28) | – |
| Pharmaceuticals only | 29.3 (24) | – |
| Both: diet and pharmaceutical | 28.0 (23) | – |
| Neither, no treatment | 8.5 (7) | – |
PKU, phenylketonuria
Demographics
The majority of individuals with PKU were currently in a long-term relationship (n = 70, 85.4%). Respondents’ ages ranged from 23 to 72, with a mean of 37 years (standard deviation (SD) = 11.9). Partners’ ages ranged from 23 to 73, with a mean of 37 years (SD = 11.7). Participants were primarily female (72.0%), who obtained college degrees (n = 55, 67.0%), worked full-time (n = 54, 65.9%), and made over $68,000 annually (n = 47, 57.3%). See Table 1 for details.
The mean RAS was 27.0 (SD = 7.1; see Fig. 1a for distribution). Participants in a current relationship had higher relationship satisfaction of 28.9 (standard error (SE) = 0.63, Fig. 1b) compared to those in a previous relationship 15.9 (SE = 1.7, p < 0.0001; Fig. 1b). There was a negative correlation of RAS with partner age (rho = − 0.27, p = 0.013, Table 2) and participant age (rho = − 0.28, p = 0.001, Table 3).
Fig. 1.
The distribution of relationship assessment scores and reported relationship status (n = 82). a Box-plot distribution of RAS from respondents. A higher score is associated with higher relationship satisfaction. b Averaged RAS by reported relationship status. RAS, relationship assessment scores. ***p < 0.001
Table 2.
Survey variables individually associated with relationship assessment score that were not significant after accounting for all variables in this and Table 3
| Variable | RAS mean, SE, *rho | Individual p-value |
|---|---|---|
| Disagreements on PKU management? | 0.0001 | |
| Yes | 24.2 (1.0) | |
| No | 31.5 (0.71) | |
| Partner health | 0.0003 | |
| Good | 29.8 (1.0) | |
| Fair | 24.4 (1.1) | |
| Poor | 20.4 (3.9) | |
| Participant health | 0.008 | |
| Good | 28.9 (0.9) | |
| Fair | 24.3 (1.3) | |
| Poor | 22.6 (3.0) | |
| Income | 0.012 | |
| > $68,000 | 28.7 (1.5) | |
| < $68,000 | 24.7 (1.4) | |
| Partner age | -0.27* | 0.013 |
| Sum of PKU straining factors | -0.24* | 0.030 |
| Phenylalanine frequency checks | 0.072 | |
| At least 1 × monthly | 30.0 (1.4) | |
| < 1 × month | 26.4 (0.9) |
RAS, relationship assessment score; SE, standard error
*Pearson correlation coefficient rho
Table 3.
Survey variables associated with relationship assessment score after accounting for all variables in Table 2 and this table
| Variable | RAS mean, (SE), *rho | Individual p-value | Type 2 p-value |
|---|---|---|---|
| Current relationship status | < 0.0001 | < 0.0001 | |
| Current (n = 70) | 28.9 (0.6) | ||
| Previous (n = 12) | 15.9 (1.7) | ||
| Has your PKU diagnosis contributed to ending previous relationship? | < 0.0001 | 0.0012 | |
| A lot | 23.3 (1.8) | ||
| Some | 23.6 (1.3) | ||
| None | 30.0 (1.0) | ||
| Age | − 0.28* | 0.001 | 0.0048 |
| Number of disagreements | − 0.46* | < 0.0001 | 0.0061 |
| Partner involvement | < 0.0001 | 0.024 | |
| Very involved | 25.9 (1.2) | ||
| Moderately involved | 23.8 (0.96) | ||
| Not involved | 21.6 (1.2) | ||
| Treatment category | 0.014 | 0.027 | |
| Diet alone | 23.0 (1.1) | ||
| Pharmaceutical alone | 22.2 (1.1) | ||
| Both (diet and pharm) | 26.1 (1.1) | ||
| Partner involvement and treatment category | 0.0012 | 0.10 |
RAS, relationship assessment score; SE, standard error
*Pearson correlation coefficient rho
Diagnosis-related factors associated with relationship satisfaction
Factors associated individually (p<0.10) with higher RAS are described in Table 2 and depicted in Supplemental Figure 1 (Online Resource 1). Participants who disagreed less with their partners on their PKU management (p=0.0001), partners and participants in better health (p=0.0003 and p=0.008 respectively), reported income over $68,000 (p=0.012), and having a partner that is older (p=0.013) had higher relationship satisfaction. Participants who reported lower numbers of factors that negatively impacted the relationship (rho = −0.24, p=0.03) and participants that checked their phenylalanine levels at least once a month had marginally higher RAS than participants who checked less frequently (30.0 and 26.4, p = 0.072). However, none of these variables predicted RAS after adjusting for all factors identified in the stepwise procedure. There was no association between phenylalanine levels (≥360 µmol/L or <360 µmol/L) and RAS (p=0.32).
Factors that predicted RAS after accounting for all other variables are described in Table 3 and depicted in Supplemental Figure 2. Individuals in a current relationship (p<0.0001) or who reported that their PKU did not contribute to the ending of a previous relationship (p=0.0012), those who were older (p=0.0048), and those who reported disagreeing less (p=0.0061) had higher relationship satisfaction. Having a partner who was more involved with managing PKU (p=0.024) and following treatment recommendations that included both diet and pharmaceutical treatment (p=0.027) had higher RAS. However, of the individuals whose partners were not involved, those that were on both types of treatments had higher relationship scores compared to those on either treatment alone (Fig. 2; interaction p=0.0012 before adjusting, p=0.10 after adjusting for all factors).
Fig. 2.
Averaged relationship assessment scores by treatment category and partner involvement (n = 82). Treatment category (diet alone, pharmaceutical alone, and both) and partnership involvement (very, moderately, and not at all involved) was compared to the averaged RAS. RAS, relationship assessment scores
Increased partner involvement was associated with higher relationship satisfaction
Individuals with partners more involved in their PKU management had higher RAS (p<0.0001 individually, p=0.024 after adjusting for all factors; Table 3, Fig. 2). Ways in which partners assisted with their PKU management the most included grocery shopping (52.9%, n=37), preparing meals (48.6%, n=34), and transportation to doctor appointments (38.6%, n=27). See Supplemental Table 4 for details (Online Resource 1). One participant described how their partner was very involved with their PKU management:
“I have been married for 26 years and my husband was and is very helpful with my PKU! I couldn't ask for anything more! He helps shop with me for food, he helps prepare meals and is very supportive!” (Married, RAS score = 35, 99th percentile)
Greater partnership involvement and following diet or pharmaceutical treatment were associated with higher relationship satisfaction
Within the treatment categories diet alone and pharmaceutical alone, increased partner involvement was associated with higher RAS (Fig. 2 and Table 3). Individuals following “both diet and pharmaceutical” treatments who also selected “not at all” for partner involvement had a significantly higher RAS, than pharmaceutical treatment alone (pairwise corrected p=0.04).
Partnership disagreements and recognition of the strain of PKU on the relationship are associated with lower relationship satisfaction
Participants who recognized that their PKU diagnosis contributed to the ending of a previous relationship or had an increased number of disagreements with their partner had a lower RAS, even after adjusting for other factors (Table 3). Specifically, participants who reported their PKU contributed “a lot” to the ending of a previous relationship had lower RAS compared to those who said “none” (RAS =23.3 versus 30.0, SE=1.8 and 1.0, pairwise corrected p=0.0053). A higher reported number of disagreements with their partner negatively impacted the relationship and was negatively correlated with RAS (rho = −0.46). The top reported disagreements involved social functions (27.2%, n=22), side effects of PKU (27.2%, n=22), and dietary restrictions (22.2%, n=18) outside of none (38.3%, n=31, Supplemental Table 5 Online Resource 1). See Supplemental Figure 3 for the distribution of the number of argument factors selected (Online Resource 1). Below are quotes taken from open-ended questions from participants further discussing the difficulties with social function attendance and having a PKU diagnosis:
“I feel like with food being such a huge social thing that having PKU makes socializing difficult. I feel like sometimes a partner would think it more as a burden than something that's easily managed and that I was too different.” (In a relationship, RAS score = 23, 30th percentile)
“Eating is a big part of forming a social connection. I feel very disconnected socially and unable to relate to a lot of situations.” (Separated, RAS score = 13, 5th percentile)
Better management of PKU lessens the impact of factors that strain the relationship
Supplemental Table 3 provides all potential factors of PKU that strained the relationship and their average impact score (Online Resource 1). The most common reported factors that strained the relationship included emotion (56.1%, n=46), finances (39.0%, n=32), and family planning (37.8%, n=31). The factors most severely impacting the relationship included family planning, eating out, and treatment management (impact mean = 1.7, lower scores indicate more severe of impact). See Supplemental Figure 4 for the distribution of the number of straining factors selected (Online Resource 1). How well PKU was managed predicted the impact of factors that strained the relationship (F(2,69)=7.25, p=0.0014) after adjusting for the phenylalanine level. Specifically, participants who managed their PKU fairly well or moderately well reported that factors had less severe of an impact (mean impact score = 1.97, SE=0.092; mean impact score = 2.09, SE=0.093 respectively) than those who managed their PKU poorly (mean impact score = 1.25, SE = 0.20; pairwise corrected p=0.0017 and p=0.021 respectively). There was no statistical significance observed between participants’ last reported phenylalanine level and severity of an impact (p=0.28). One participant described the difficulties with maintaining blood levels and its impact on their relationships:
“I had really high blood levels and as a result experienced alot of mental health symptoms and I believe that severely impacted my relationships and the quality of the people I choose to be with in relationships as well as the content of arguments etc.” (In a relationship, RAS score = 32, 70th percentile)
Diet and/or pharmaceutical treatment improve phenylalanine levels and lessen the impact of factors that strain the relationship
Participants who reported treating their PKU with a pharmaceutical alone or both a pharmaceutical and diet treatment/s were slightly more likely to report their last phenylalanine level to be <360 µmol/L than participants on diet alone or no treatment (p=0.029) (Fig. 3). When participants followed treatments involving both diet and a pharmaceutical, their averaged impact score was significantly higher than those on no treatment (higher impact score indicates less severe of impact; 6.1 vs 2.9; SE=0.57 and 0.96; p=0.024, Table 4). In addition, participants who were on a pharmaceutical alone or both diet and a pharmaceutical were marginally more likely to be following all recommended treatments than those on diet alone (p=0.08). As demonstrated by the below open-ended response, starting a pharmaceutical treatment assisted greatly with the side effects of PKU and stress in their relationship:
“Before beginning Kuvan about 9 years ago, I was having a lot of mood swings and had very poor memory. They both contributed to stress and the relationship ending.” (In a relationship, RAS score = 31, 60th percentile)
Fig. 3.
Percentage of respondents by last phenylalanine level and treatment category (n = 82). The percentage of participants in each treatment category and their last phenylalanine level. Respondents following pharmaceuticals alone or both pharmaceutical and diet were slightly more likely to report lower phenylalanine levels than respondents on diet only or no treatment
Table 4.
Participant reported impact score and treatment category
| Treatment category | Impact score | p-value | |
|---|---|---|---|
| Average | SE | ||
| Diet only | 5.3 | 0.52 | 0.11 |
| Pharmaceutical only | 5.2 | 0.55 | 0.15 |
| Both: diet and pharmaceutical | 6.1 | 0.57 | 0.024 |
| Neither: no treatment | 2.9 | 0.96 | – |
The impact score is the averaged severity for all straining factors selected by participants. The severity of impact ranged from severely impacted to slightly impacted (1–3). Lower scores indicate higher impact. When participants followed treatments involving both diet and a pharmaceutical, their averaged impact score was significantly higher than those on no treatment (higher impact score indicates less severe impact; p = 0.024; Bonferroni-corrected p-values for post hoc pairwise comparisons between treatment category to no treatment)
In our survey, all participants who reported their relationship status to be divorced had transitioned their treatment to pegvaliase (Palynziq®) during their relationship (n=3). One participant described this observation and how starting a new pharmaceutical treatment impacted their marriage:
“I also feel PKU makes me a less confrontational person when I should be at times. Maybe I would have gotten out of a bad marriage of 20 years sooner. Now engaged to be married but this partner has only known me since I've been on Palynziq and levels have been great!” (Divorced, RAS score = 7, 1st percentile)
Participant’s recognition of the contribution of PKU on the relationship
Participants could elaborate further on how their PKU diagnosis had impacted their relationship (37 responses were received, Supplemental Table 6, Online Resource 1). Some examples of responses are provided below:
“Negatively, the mental and emotional issues that stem from my pku has been all consuming in my life.” (Married, RAS score = 28, 45th percentile)
“I had people break up with me for just having PKU and other couldn’t deal with the time and social impact for taking care of my PKU through a highly restricted diet etc.” (In a relationship, RAS score = 29, 50th percentile)
“It seems to increase anxiety, especially around taking meds/formula around in-laws, family planning and obtaining prenatal genetic counseling. I also am harder on myself I experience a high level because I feel that it no longer impacts just me, it impacts my spouse, our relationship and our future family.” (Married, RAS score = 33, 80th percentile)
Discussion
To our knowledge, this is the first study to examine relationship satisfaction in individuals with a metabolic condition and to explore how lifestyle, management, and treatments of this condition play a role in partnership happiness. We found that increased relationship satisfaction is associated with following recommended treatment, having a partner involved in management, and recognizing the PKU diagnosis played a role in the ending of a previous relationship. We observed that good health in both the patient and partner is associated with higher relationship satisfaction. This result confirms previous studies demonstrating that better partner and personal health correlates with higher relationship satisfaction in patients with a chronic illness (Baucom et al. 2020; Downward et al. 2022). This stresses the importance of health not only in the participant, but also in their partner.
Participants following treatments involving both a diet and pharmaceuticals reported lower impact of straining factors on their relationship and were found to have higher relationship satisfaction than those on diet alone. Adherence to dietary restriction recommendations is difficult (Ford et al. 2018; Rose et al. 2019; Zurflüh et al. 2008), and as a result, many patients with PKU endure suboptimal outcomes and encounter prevalent neuropsychological and psychosocial difficulties (Aitkenhead et al. 2021; Bilder et al. 2013; Enns et al. 2010; Jahja et al. 2016, 2017). Taken together, these findings suggest that pharmaceutical treatments offer greater ease of compliance, more successful long-term management of PKU, and potentially lower negative impact of PKU on a relationship. Of note, newer treatments may allow for increase in protein consumption and do not require as challenging of dietary restrictions.
All patients who reported their relationship status to be divorced had begun a new pharmaceutical treatment, pegvaliase, during their previous relationship. These respondents attributed a large motivator in their choice to divorce was that the newer treatment greatly reduced their symptoms of poorly controlled PKU (such as difficulty with cognition, memory, mental health complications), and they were no longer satisfied with that partner. Although there are no studies documenting a link between marital status and change in treatment to pegvaliase, the clinic staff at Indiana University anecdotally observed multiple patients, who after switching to pegvaliase, had divorced their long-term partner. While this might have clinical implications on how to advise patients making this switch, it is important to note that our study is biased for current rather than previous relationships, and there was a low response rate of divorced respondents.
It is well-reported that chronic illnesses pose unique challenges to patients and put additive strain on relationships (Joung et al. 1998; Wilson and Waddoups 2002). In our study, the predominant factor straining the long-term relationship was emotion. This aligns with Marcus et al.’s (2013) findings where heightened mood disturbances in patients with fibromyalgia reported lower relationship satisfaction via the Relationship Assessment Scale (Hendrick 1988). Within the PKU community, Ford et al. (2018) found that 31% of their respondents experienced relationship implications tied to diagnostic challenges. Similarly, our study found that close to half of respondents reported their PKU had contributed either “a lot, or a little” to the ending of a previous relationship, and the majority reported their PKU contributed to issues in a previous long-term relationship. These trends highlight the impactful role chronic illness has in shaping relationship dynamics.
Among the reported neuropsychological outcomes in patients within the PKU community, the persistence of emotional perturbations (i.e., mood disturbances, depression) is a recurrent theme (Jahja et al. 2017; Pietz et al. 1997; Quinn et al. 2022). Importantly, our study supports this theme as emotion was the most common relationship challenge between couples, followed by finances and family planning. Management of PKU can also affect relationship challenges. Aitkenhead et al. (2021) found that those with partial adherence to a PKU diet reported a significantly poorer quality of life than those who were confident in their management. Similarly, our results demonstrated that those who reported their level of management of PKU as being “high” also reported the lowest degree of impact of PKU-related challenges on their relationship. This provides insight to the importance of management of PKU and the neuropsychological aspects encompassing mood, emotion, and anxiety.
The financial impact and discomfort with attending social-functions due to their PKU are also a concern with this population (Bik-Multanowski et al. 2008; MacDonald et al. 2010; Rose et al. 2019). Family planning is a unique challenge associated with PKU, as all women with PKU and hyperphenylalaninemia are recommended to receive reproduction counseling due to the teratogenic effects of high phenylalanine levels during a pregnancy. Estecha Querol et al. (2020) found that for those with chronic illness, the four main themes of concern included chronic illness as a disruptive experience, finances, lifestyle and health risks, and reflections on current inequalities. Our findings further support that finances and lifestyle and health risks (neuropsychologic disturbances, risk of maternal PKU and pregnancy) are top areas of strain in a relationship in adults with PKU.
Strengths and limitations
The primary strengths of this study are the novel insight into relationship satisfaction of individuals with PKU, factors affecting that relationship, and the generalizability of these results to other chronic disorders. However, there are several limitations. One limitation of our study is that there was only a small number of participants, and participants were largely female and held college degrees. Therefore, this sample may not be representative of the overall demographic of patients with PKU. Although the relationship scale was validated, it has not been validated in a PKU population. Respondents self-reported medical and PKU management information including their health, recent medical treatment recommendations, and their partner’s health, which have no means of independent verification. In addition, we did not collect information on the age at which treatment began, which could have affected cognitive performance and relationship involvement. It is possible there was bias towards respondents that were in more satisfying relationships, as those who were not may have declined to participate in the survey. Therefore, participants that were single and in a lower-satisfied relationship may be under-represented in this survey. We did not utilize a validated survey on factors related to PKU as currently one does not currently exist. Lastly, as this was an exploratory study, we did not collect any control data from the general population.
Conclusions
Our findings are not specific to only the PKU community but can be applied to other groups with chronic illnesses (e.g., chronic fatigue, diabetes) which require daily treatments, display symptoms that can impede daily activities, and carry diagnostic-specific challenges. The downstream effects of stronger adherence to treatment, partner involvement, and reduction of straining factors due to a diagnosis can all be applied to further increase relationship satisfaction in these groups. In addition, we found that newer treatment options were associated with lower severity of impact of PKU-related factors and higher relationship satisfaction. These newer treatment options provide greater ease of compliance and correlate with more successful long-term management, both of which increased relationship satisfaction. Providers could incorporate discussions on patient’s support systems and explore their partner’s involvement in disease management.
These results should be used by healthcare providers to prepare patients for management compliance and discussion around treatment options as adults. In addition, our study underscores the need for further research and the creation of a validated questionnaire specifically tailored for PKU to assess relationships, as this would be a valuable tool to assist in the healthcare practice of this population. This allows for further discussion on the importance of adherence to treatment and its role in relationship satisfaction. Addressing the gaps in research for underserved populations, such as those with metabolic conditions or chronic illnesses, is incredibly important to better provide resources, support, and education to these populations. If we can prepare, or at minimum notify them, of the unique difficulties ahead, we can better utilize support services to help our patients navigate all stages of life with a diagnosis.
Supplementary Information
Below is the link to the electronic supplementary material.
Acknowledgements
The authors would like to thank the various support groups, the National PKU Alliance, and clinics that facilitated the distribution of the survey, as well as the patients with PKU who participated in the study. We would also like to acknowledge the Indiana University School of Medicine Genetic Counseling Graduate Program for providing funding for the gift card incentive. This work fulfilled a degree requirement for the first author, who was in training while the research was conducted.
Author contribution
Rachel Sundstrom was responsible for the acquisition of funding, dissemination of recruitment materials, and the initial draft of the manuscript. Leah Wetherill provided data analysis and interpretation. Katie Sapp and Rachel Sundstrom conceptualized the project. All the authors were involved in the development of methodology, writing, reviewing, editing of the manuscript, and approval of the final draft.
Data availability
The datasets generated during and/or analysed during the current study are available from the corresponding author on reasonable request.
Declarations
Ethics approval
All procedures followed were in accordance with the ethical standards of the responsible committee on human experimentation (institutional and national) and with the Helsinki Declaration of 1975, as revised in 2000 (5).
Informed consent
Informed consent was obtained from all patients for being included in the study.
Conflict of interest
Melissa Lah is a primary investigator on clinical trials for PKU with BioMarin Pharmaceutical Inc., Homology Medicines Inc. and PTC Therapeutics. Melissa Lah also serves on Palynziq related advisory boards for BioMarin Pharmaceutical Inc.
Rachel Sundstrom, Leah Wetherill, Katie Sapp, and Molly McPheron declare that they have no conflict of interest.
Footnotes
Publisher's Note
Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.
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Associated Data
This section collects any data citations, data availability statements, or supplementary materials included in this article.
Supplementary Materials
Data Availability Statement
The datasets generated during and/or analysed during the current study are available from the corresponding author on reasonable request.