Evaluation of quality of life, muscle and cardiac involvement and neurologicaldevelopmental status of infantile pompe patients followed up in A pediatricmetabolism and nutrition clinic

Evaluation of Quality of Life, Muscle and Cardiac Involvement and Neurological Developmental Status of Infantile Pompe Patients Followed up in a Pediatric Metabolism and Nutrition Clinic Aim: The aim of this study is to evaluate the demographic, clinical and molecular findings, pretreatment and posttreatment parameters related to cardiac functions, cognitive status, longitudinal motor assessment and quality of life of infantile Pompe patients, who are followed up and treated with enzyme replacement therapy in Çukurova University Medical Faculty Pediatric Metabolism and Nutrition Department. Material and Method: In this study, 42 infantile Pompe patients who were diagnosed with molecular analysis or acid alpha-glucosidase enzyme analysis and followed up in between 2009 and 2020 in Çukurova University Medical Faculty Pediatric Metabolism and Nutrition Department were included. Retrospectively, demographic features, personal and family histories, clinical findings, laboratory data, enzyme analysis, molecular findings, duration of enzyme replacement therapy, and survival of patients were assessed. Patients were grouped as classical and non-classical infantile Pompe disease and CRIM status were interpreted according to genotype. Also, creatinine kinase (CK) levels, echocardiography, cardiac rhythm analysis with 24-hour Holter electrocardiogram, gross motor functions, myotonometric measurements, 10 meter walk test, 6 minute walk test, 3 minute step test, muscle strength, quick motor functions test (QMFT), bone mineral density (BMD) and muscle mass measurements with dual energy x-ray absorptiometry (DXA) of 22 patients who were able to be mobilized independently in the last visit were evaluated. Quality of life assessments were done with Pediatric Quality of Life (PedsQoL) Inventory including parent and child forms. Neurocognitive assessments were done with Denver II Developmental Scale, Stanford Binet Intelligence Scales, and Wechsler Intelligence Scale for Children (WISC-R) according to the patient's age. Audiological evaluations were done. Vitamin B12 and D and folic acid levels were measured. Findings: 50% of the 42 infantile Pompe patients were female. 40,5% of the patients have deceased. The mean current age of 25 alive patients was 66,5±28,3 (16,1- 124,0) months. None of the patients in the non-classical group have died. At the last visit, 96% of these patients were mobile and 75% of the mobile patients were mobilized independently. 15 of 22 mobile patients (68,2%) were classical type infantile Pompe patients. All of the patients were on enzyme replacement therapy (ERT) with the dose of 40 mg/kg/2 weeks. Hypertrophic cardiomyopathy findings were regressed after 15,3±9,1 (3,6-32) months of ERT in all patients. 6 patients had cardiac arrhythmia. There were not any change in CK levels related to therapy. Comparison of gross motor functions, myotonometric measurements, and functional status assessments of patients in 2018 and currently indicated that functional capacity of the patients were preserved. This highlighted that, ERT has beneficial effects on both cardiac and skeletal muscle functions. Also, mobility rates and functional capacity of the patients in non-classical group were better compared to classical group. BMD measurements with DXA detected z scores below - 2 SD in 5 patients. Body fat was measured with DXA. 60% of 10 patients have increased adipose tissue mass compared to age-matched healthy Turkish children. 9 patients (41%) have hearing impairment. 45% have sensorineural, 33% have conductive, and 22% have mixed hearing loss. 8 of these patients have speech problems. Neurocognitive assessments showed (Stanford Binet and WISC-R) borderline intelligence in 9 of 15 patients (60%). Denver II Developmental Scale were abnormal in 7 patients. Quality of life scores were higher in mobile and non-classical patients. Conclusion: Infantile Pompe disease is a rare inherited metabolic disease. ERT have positive effects on survival, functional capacity, quality of life and cardiac findings of the patients. With 42 patients and for 11 years in a single center, we have showed that high dosage ERT have decreased mortality and morbidity in our patients. With 61,0±32,6 (10,7-124,7) months ERT, cardiac findings were completely resolved, functional capacity of the patients were preserved and positive effects on quality of life of both patients and parents were observed. This study is a single center study including cardiac findings, enzyme analysis, genotype, cognitive and motor functions, audiological evaluations, BMD, adipose tissue mass and quality of life assessments of a large group of infantile Pompe patients.