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

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 40 infants at Duke that has screened for LOPD. This study
involves minimal risk to the patient and offers a potential benefit of improved disease
management. The initial visit will be as soon as possible after a confirmed LOPD diagnosis
and follow up visits will be at 6 and 12 months. The investigators will continue to gather
clinical information on patients and monitor clinical status beyond assessment at three time
points.

The study has three goals:

1. To study and record disease specific clinical symptoms in newborns and infants with
Pompe disease without cardiomyopathy (disease of the heart muscle) 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

3. To determine criteria to start preventative therapies including enzyme replacement
therapy (ERT) in patients with clinical features of Pompe disease identified 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 18 months