Assessment of neurological morbidity and psychiatric disease burden with metabqol 1.0 questionnaire in organic acidemias

Organic acidemias are rare inherited metabolic diseases caused by enzyme deficiencies in various neurometabolic pathways. Phenotypic expression depends on residual enzyme activity, age of onset, accumulation of toxic endogenous metabolites (organic acids and derivatives), permeability of the blood-brain barrier, interactions of the mutated gene with other genes or the environment. Long term neurological complications and/or comorbidities include intellectual disability, seizures, movement disorders (dystonia, choreoathetosis, spasticity or ataxia), behavioral and psychiatric problems. MetabQoL 1.0 is the first disease-specific quality of life questionnaire for patients with intoxication-type inborn errors of metabolism. It is translated to our language. Our aim was to assess the validity and reliability of the MetabQoL 1.0 questionnaire, and neurological morbidity and/or psychiatric burden in our patients with methylmalonic acidemia (MMA), propionic acidemia (PA) and isovaleric acidemia (IVA). In order to evaluate the validity and reliability of MetabQoL 1.0 we used Pediatric Quality of Life (PedsQOL) for comparison. Data on 29 patients aged 8- 18 years with the diagnosis of MMA, PA and IVA and their parents were included in the study. Patients were followed up at a single center, Hacettepe University İhsan Doğramacı Children's Hospital Department of Pediatrics, Division of Metabolism and Nutrition. Twenty-two of these patients were evaluated at the hospital, whereas seven of the patients received the questionnaire through a phone call. The mean age of the cohort was 12.62 years (± 3.4). Seventeen of the patients were female, and 12 were male. MetabQoL 1.0 questionnaire was shown to be valid and safe (Cronbach's alpha coefficients 0.64-0.9). There were positive neurological examination findings in 63.6% (n=14) of the patients. Among 20 of the 22 patients evaluated formally, 17 had a psychiatric disorder (85%). Physical, cognitive, and overall score medians of the MetabQoL 1.0 questionnaire were lower on child scales compared to the parentreported scores. The median scores of the parents' were significantly higher than the children's (p=0.023). The median severity score of the children's was higher than the parents (p=0.011). A significant difference was found between the diagnostic groups in terms of parental social score (p= 0.017). Accordingly, parental social score median of the IVA group was significantly higher than the other two diagnostic groups. A significant difference was found between the parental social score (p=0.041) and total score (p=0.025) in patients with global developmental delay and intellectual disability. The median parental social and total score of the patients with developmental delay were lower (64.2/68.2, respectively) compared to the patients without developmental delay (75/82.6, respectively). When patients in the groups with early and late diagnosis were compared, significant differences were found between MetabQoL 1.0 questionnaire parent physical score (p=0,008), cognitive score (p=0,042), total score (p=0,022), and child social and total scores. Median parental physical, cognitive and total score of patients with a late diagnosis (66.3/81.2/68.2, respectively) were found to be lower than the patients with an early diagnosis (80.7/91.6/80.7, respectively). Median child social and total scores of patients with late diagnosis were found to be lower than those with early diagnosis (73.2/61.5 and 92.8/78.8, respectively). There was no significant relationship between the age of onset of symptoms, diagnostic group, neurological findings of the patients, seizures and HRQoL. The lack of difference between chronic disease burden and quality of life scales in patients with neurological and psychiatric morbidity may reflect parental focus on metabolic disease rather than comorbidities. The differences depending on the time of diagnosis emphasize the importance of early diagnosis. Intoxication-type metabolic diseases are a group of diseases in which some findings can be controlled with appropriate metabolic management, but have high neurological and/or psychiatric morbidity. To the best of our knowledge, the MetabQoL 1.0 questionnaire was applied for the first time in a different language and patient population beyond the original description. Evaluation of quality of life by patients and their parents covering different aspects will gain importance as one of the outcome measures in clinical follow-up and future research studies. Awareness of disease-specific patient and parent reported outcomes highlight the importance of in depth understanding of long-term comorbidities, teamwork, and prioritization of appropriate education and rehabilitation programs.