Determination of contribution of clinical markers to diagnosis in cases considering juvenile pompe disease

Introduction: Pompe Disease is a progressive muscle disease with a wide phenotypic distribution caused by an inherited deficiency of the acid alpha glucosidase enzyme. Acid alpha glucosidase enzyme deficiency causes cell damage and organ dysfunction due to excessive accumulation of glycogen in lysosomes. The gene region responsible for this disease, which is inherited as an autosomal recessive, is 17q25. The age of onset of the signs and symptoms of Pompe Disease, which has an incidence varying between 1/33.000 and 1/300.000, varies significantly between patients. Acid alpha glucosidase enzyme activity has been detected below 1% in Infantile-Onset Pompe Disease and excessive glycogen accumulation often results in death under 1 year of age. Infantile Onset Pompe Disease is characterized by cardiomyopathy and hypotonia. Respiratory distress due to diaphragm dysfunction, mild hepatomegaly, macroglossia, increased frequency of upper respiratory tract infections, motor developmental retardation, feeding difficulties can be encountered in infantile form. The late-onset form, whose acid alpha glucosidase enzyme activity varies between 1% and 40%, shows a slower course compared to infant cases. It presents with different clinical findings such as cardiovascular insufficiency, myopathy, muscle weakness, muscle atrophy, bulbar and cranial nerve involvement signs, scoliosis, growth and development retardation, respiratory distress. and a heterogeneous clinical course can be observed among the cases. Symptoms and signs of Late-Onset Pompe Disease can easily be confused with many diseases and patients cannot be diagnosed for many years. Therefore, it becomes important to what extent the clinical findings contribute to the diagnosis and in which cases Pompe disease should be investigated. Enzyme replacement therapy with "alglucosidase alfa" has been used in patients diagnosed with Pompe disease since 2006. Alglucosidase alfa treatment is an effective treatment method that is generally well tolerated by the patients and slows the progression of the disease in Late-Onset Pompe patients. With this treatment, the life span of infant patients was extended, and clinical improvement or stabilization was achieved in Late-Onset Pompe patients. The aim of this study was to study proximal, axial, respiratory muscle weakness of unknown cause, ptosis, rigid spine, asymptomatic creatine kinase elevation, cardiomegaly and hypotonia between the ages of 12 months and 18 years who were admitted to the Pediatrics and Pediatric Neurology outpatient clinics at Dokuz Eylül University Medical Faculty Hospital. The purpose of this study is to investigate the contribution of clinical markers to the diagnosis in order to provide early diagnosis of Late Onset Pompe Disease. Materials and Methods: This study was conducted with the patients that have symptoms of myopathy, muscle weakness, muscle atrophy, bulbar and cranial nerve involvement findings, scoliosis, growth retardation, respiratory distress, cardiovascular failure findings. One hundred volunteers among the patients who were sent alpha glucosidase enzyme analysis were included. Patients younger than 12 months and older than 18 years and those with any neuromuscular or metabolic disease were excluded from the study. Results: Acid alpha glucosidase enzyme analysis was studied by applying the symptom evaluation questionnaire to 100 patients aged between 12 months and 18 years with no specific disease diagnosis and have myopathy, muscle weakness, muscle atrophy, bulbar and cranial nerve involvement findings, scoliosis, growth and development retardation, respiratory distress, cardiovascular failure who applied to the Dokuz Eylül University Medical Faculty Pediatric Neurology outpatient clinic. 64% of the cases are male and 36% are female. Creatine kinase elevation is present in 50% of the cases. The most common findings were 32% weakness in the proximal lower extremity, 27% exercise intolerance, and 20% weakness in the proximal upper extremity. A low level of acid alpha glucosidase enzyme or mutation in the enzyme gene was not detected. However, 4 patients were diagnosed with Duchenne Muscular Dystrophy, 1 patient with Becker Muscular Dystrophy, 1 patient with Congenital Muscular Dystrophy, 1 patient with Limb Girdle Muscular Dystrophy. Conclusion: Unlike Infantile Onset Pompe Disease, Late Onset Pompe Disease has a milder clinical course and these cases cannot be diagnosed until adulthood. Late-onset Pompe disease should be one of the pre-diagnoses to be considered in the presence of ambiguous complaints such as fatigue, cramps, and complaints and findings suggesting muscle weakness. Multi-center, national studies are needed to identify clinical markers for diagnosis. Keywords: Asid alpha glucosidase, Late Onset Pompe Disease, muscle weakness.