Health-Related Quality of Life in Children and Families Affected by Methylmalonic Acidemia
Knowledge of the psychosocial impact of methylmalonic acidemia (MMA) on children and families is necessary in planning counseling and therapeutic intervention. Although clinical outcomes of MMA have been reported, research on its psychosocial impact is limited.
In recent years, liver transplantation (LT) and combined liver-kidney transplantation (LKT) have been used as treatment options for patients with MMA mut0 with the goal of preventing hyperammonemia and metabolic ketoacidosis. After LT, patients have demonstrated increased energy, muscle strength, mobility, and protein tolerance; however, neurologic damage, kidney disease, graft loss, and death as a result of acidosis and sepsis have also been described post-LT. Given the varied outcomes, LT is not considered curative and there are ongoing efforts to determine its most appropriate role in the management of children with MMA.
The goal of this study was therefore twofold: (1) to measure health related quality of life (HRQoL) in children and families affected by MMA using the Pediatric Quality of Life Inventory (PedsQLTM) parent version and free responses, and (2) to assess the impact of LT on HRQoL by comparing responses between LT and non-LT patients.
From November 2013 to February 2014, parents and caregivers of children with MMA were invited to participate in a survey through the Organic Acidemia Association (OAA), an MMA Facebook group, the Stanford Children’s Hospital biochemical genetics clinic, and members of the Metab-L mailing list. To be eligible for the study, participants were required to be a parent/caregiver of a child between ages 2 and 18 years with a reported diagnosis of MMA
mut0.
A total of 35 responses from parents/caregivers of children (16 males, 19 females, mean age= 8.0 years) with a reported diagnosis of MMA mut0 were received. 71.4% of responses were from English-speaking parents/caregivers and 28.6% were from Japanese-speaking parents/caregivers. 45.7% of responses were from parents/caregivers of children with LT (7 males, 9 females, mean age= 8.4 years). Mean age at time of diagnosis was less than one year and mean age at time of transplant was 3.3 years. Of the post-transplant sample, 62.5% of respondents reported that their child underwent only LT and 31.3% reported that their child underwent LKT. 25.0% of respondents reported post-transplant complications.
Parents/caregivers were asked to select the MMA related interventions that their child receives. 75% of post-LT respondents reported that their child requires feeding by G-tube, whereas only 42.1% of non-LT respondents reported G-tube feedings. 31.3% of post-transplant respondents reported that their child requires hemodialysis, whereas only 5.3% of non-transplant respondents reported the use of hemodialysis.
Parents/caregivers reported lower scores on the majority of the PedsQLTM scales as compared to samples of healthy children, children with solid organ transplants for indications other than MMA, and families affected by chronic conditions. Scores for children with MMA were lowest in school and social functioning. Scores for families were lowest in worry and activity impairment. In free responses, parents/caregivers expressed that worry and impairment of daily activities, like family social activities, were caused by the potential for metabolic decompensation.
Recurring concepts in parent/caregiver free responses about the psychosocial impact of MMA on the family included a better perspective on life, increased family member anxiety, stronger family bonds, social isolation, strains on family relationships, a general negative impact on the parents and child, and financial burden.
No significant differences were observed when scores from the PedsQLTM scales were compared between children with and without LT. However, when asked, “In your opinion, did the transplant positively or negatively affect your child’s development,” the majority (93%) of parents/ caregivers of children post-LT responded that the transplant had had a positive impact on their child’s development. Six recurring concepts about the impact of the transplant were identified from these responses, including health-related improvement, increased family social involvement, decrease in parental anxiety, a more positive outlook, and intellectual and emotional improvements in the child.
The majority of parents/caregivers reported positive impacts of LT in free responses. This positive perception of quality of life post-LT is similar to results from other studies of children with MMA post-LT. The discrepancy between scores on standardized HRQoL modules and parent reports may reflect greater disease severity in children post-LT as compared to children without LT. Children post-LT may have had more severe symptoms pre-transplant, leading to the decision for transplantation. The children with LT had a higher reported use of G-tube feeding and dialysis, suggesting that this group may have had more severe symptoms that necessitated these interventions. To control for these possible differences in disease severity, it would be helpful to administer standardized HRQoL modules before and after LT to the same patient/ family in future studies.
In summary, this study was the first to query parents/caregivers regarding the impact of both MMA and LT on the HRQoL of their children and families using standard measures and presents the largest sample of children with MMA post-LT published to date. The results show a negative impact of MMA mut0 on patient and family HRQoL. In particular, school functioning and social interactions are impaired in children and daily activities, like family activities and household tasks, are impaired in families. There were no significant differences in LT and non-LT patient scores on the standardized HRQoL scales, yet the majority of parents/caregivers reported positive impacts of LT in free responses. Findings such as these from HRQoL studies should be combined with developmental and medical outcome measures when considering LT as a treatment for children with MMA mut0.
We want to sincerely thank all of the families who participated in this project, and the Organic Acidemia Association for putting us in touch with many of those families.
Kimberly Splinter, MS, CGC
Genetic Counselor and Project Manager
Undiagnosed Diseases Network
Harvard Medical School
From the Spring 2016 OAA Newsletter