Developing a Management Approach for Patients With Late-Onset Pompe Disease

Study Overview
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Brief Summary
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This is an observational study with no study related treatment of interventions. The purpose of the study is to investigate and document disease specific clinical symptoms in newborns, infants and children with Pompe disease without cardiomyopathy identified in newborn screening(NBS). There will be baseline, months 6 and months 12 visits for infants and newborns (infants study). For children of ages 24 months to 54 months, there will be baseline, year 1 and year 2 visits (children study). The study has four goals: To study and record disease specific clinical symptoms in newborns, infants and children with Pompe disease without cardiomyopathy (disease of the heart muscle) in the first year of life identified through newborn screening (NBS) To devise an approach to characterize early musculoskeletal (muscles and joints) involvement in subjects with the late-onset GAA variant identified by NBS including ability to collect research information via virtual health platforms. To determine criteria to start preventative therapies including enzyme replacement therapy (ERT) in patients with clinical features of Pompe disease identified via NBS To document parental coping and anxiety/emotional distress overtime using quality of life questionnaires after a child is diagnosed with late onset Pompe disease via NBS

Detailed Description
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Late-Onset Pompe Disease(LOPD) is an inherited disorder caused by lack of or defect in the enzyme acid alpha-glucosidase (GAA). GAA enzyme deficiency causes glycogen to build up and damage cells throughout the body, especially in the heart and muscles. In LOPD, subtle and overt disease-specific features may go unrecognized in childhood without vigilant clinical examination and assessments with appropriate functional tests. In our clinical experience, children with the late-onset GAA variant may present much earlier in life and adult patients with LOPD consistently report a much earlier symptom onset and a significant diagnostic delay. These patients have shown improvement after initiation of ERT but have motor impairments adversely affecting their quality of life and growth from early childhood. Therefore, earlier diagnosis and initiation of ERT is crucial in these patients. Instituting ERT at an ideal time may prevent/reduce these irreversible musculoskeletal impairments and lead to a better quality of life and less disease burden as these children age. Our team of Pompe disease experts will perform detailed clinical evaluations, physical therapy evaluations, cardiac assessments, speech and swallow evaluations, biochemical tests, sleep questionnaire, and hearing assessments on these patients. These assessments will allow use to capture and describe the earlier clinical phenotype in these patients and provide insights into the early signs and symptoms of LOPD.This study will provide and evidence-based approach to clinical management of newborns with LOPD to primary care physicians and geneticists, leading to improves patient outcomes. The investigators will enroll 20 infants and children at Duke that has screened for LOPD. This study involves minimal risk to the patient and offers a potential benefit of improved disease management. For infants, the initial visit will be as soon as possible after a confirmed LOPD diagnosis and follow up visits will be at 6 months and 12 months. The investigators will continue to gather clinical information on patients and monitor clinical status beyond assessment at three time points. For children of ages 24 months to 54 months, there will be baseline, year 1 and year 2 visits. The study has four goals: To study and record disease specific clinical symptoms in newborns, infants and children with Pompe disease without cardiomyopathy (disease of the heart muscle) in the first year of life identified through newborn screening (NBS) To devise an approach to characterize early musculoskeletal (muscles and joints) involvement in subjects with the late-onset GAA variant identified by NBS including ability to collect research information via virtual health platforms. To determine criteria to start preventative therapies including enzyme replacement therapy (ERT) in patients with clinical features of Pompe disease identified via NBS To document parental coping and anxiety/emotional distress overtime using quality of life questionnaires after a child is diagnosed with late onset Pompe disease via NBS

Official Title
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Developing a Management Approach for Patients With Late-Onset Pompe Disease GAA Variant Identified by Newborn Screening

Conditions
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GAA Deficiency, Pompe Disease, Pompe Disease (Late-onset)

Intervention / Treatment
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* Other: Observational


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Subject has been diagnosed via newborn screening Subject has a confirmed and documented diagnosis of Pompe disease and absence of cardiac involvement Subject has predicted late-onset GAA variants such as c.-32-13T>G, c.2188G>T, c.1935C>A, c.1726G>A, c.118C>T etc. in homozygosity or compound heterozygosity Subject must be between 3 and 20 months for infant study or between 24 and 54 months (+/- 3 months) for children study at time of enrollment.

Ages Eligible for Study
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Minimum Age: 3 Months
Maximum Age: 54 Months

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Late-Onset Pompe disease<br>Individuals with a confirmed diagnosis of Late-Onset Pompe disease via NBS | Other: Observational<br>* This study is a systematic investigation of the natural history of late-onset Pompe disease in infancy and childhood<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Medical records will be tracked for up to 4.5 years to document subtle musculoskeletal signs of Pompe disease. | This outcome measure will be tested individually by a formal physical therapy assessment, Alberta Infant Motor Scale (AIMS), Gross Motor Functional Measure (GMFM), Hammersmith Functional Motor Scale Expanded(HFMSE),Modified Hammersmith Functional Motor Scale Extend(MHMFS-EXTEND), and Children's Hospital of Philadelphia Infant Test of Neuromuscular Disorders(CHOP INTEND) to give a combined assessment score. | 4.5 years | 
| Medical records will be tracked for up to 4.5 years years to document Pompe-specific clinical symptoms. | This outcome measure will be tested individually by physical examination, nutritional evaluation and functional assessment to give a combined analysis of Pompe-specific symptoms. | 4.5 years | 
| Medical records will be tracked for 4.5 years to document elevation in Pompe-specific biomarkers from blood and urine samples. | This outcome measure will be tested by comparing lab results to lab-specific ranges. | 4.5 years | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Medical records will be tracked for 4.5 years to document sleep quality. | This outcome measure will be tested qualitatively by questionnaire. | 4.5 years | 
| Medical records will be tracked for 4.5 years to document auditory capacity. | This outcome measure will be tested individually by visual reinforcement audiology (VRA) and distortion product optoacoustic emissions (DPOAE) to give a combined assessment score. | 4.5 years | 
| Medical records will be tracked for 4.5 years to document cardiac involvement. | This outcome measure will be analyzed by echocardiogram and electrocardiogram results. | 4.5 years | 
| Medical records will be tracked for 4.5 years to document muscle architecture of the calves, para-spinal muscles and tongue | This outcome measure will be tested qualitatively by simple ultrasound examination. | 4.5 years | 
| Medical records will be tracked for 4.5 years to document speech and swallow progression | This outcome measure will be tested individually by using videofluoroscopic study, Preschool Language Scale-Fourth Edition(PLS4), Receptive-Expressive Emergent Language Test Third Edition(REEL3), Pediatric Eating Assessment Tool (PEDI EAT-10), Functional Oral Intake Scale(FOIS) and serial photographs to give a combined assessment score. | 4.5 years | 
| Change in parental coping overtime using quality of life questionnaires after a child is diagnosed with late onset Pompe disease via NBS. | BRIEF COPE is completed by the patient's parent or guardian. BRIEF COPE is rated on a scale of 1-4 with 1 = 'I haven't been doing this at all' and 4 = 'I've been doing this a lot'. | yearly, up to 4.5 years | 
| Change in parent's emotional distress overtime using PROMIS questionnaire | The PROMIS questionnaire is completed by the patient's parent or guardian. Emotional distress is rated on a scale of 1-5 with 1=never and 5=always. | yearly, up to 4.5 years | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Pompe disease, Glycogen Storage Disease Type II, Acid Maltase Deficiency, Acid Alpha-Glucosidase Deficiency, Alglucosidase alfa, Newborn Screening