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

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

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:

1. 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)
2. 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.
3. To determine criteria to start preventative therapies including enzyme replacement therapy (ERT) in patients with clinical features of Pompe disease identified via NBS
4. 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

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:

1. 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)
2. 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.
3. To determine criteria to start preventative therapies including enzyme replacement therapy (ERT) in patients with clinical features of Pompe disease identified via NBS
4. 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

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.