A retrospective longitudinal study and comprehensive review of adult patients with glycogen storage disease type III.

As a clinical biochemical geneticist and a director of the Duke Biochemical Genetics laboratory, my research interests are focused on improving laboratory diagnostics for rare inherited disorders of metabolism. I am actively involved in the development of assays using mass spectrometry and other analytical techniques. My current research on biomarkers for lysosomal storage disorders, such as Fabry and Pompe disease and the mucopolysaccharidoses includes monitoring the response to novel therapies in patients. I also have an interest in neurometabolic disorders such as the creatine deficiency syndromes and sulfite oxidase and molybdenum cofactors. These disorders can be diagnosed using liquid chromatography-tandem mass spectrometric assays that measure biomarkers in urine. Guanidinoacetate methyltransferase deficiency is a disorder that can be detected in the newborn period and is amenable to dietary therapy, and is thus a good candidate for newborn screening.

Laura E Case, PT, DPT, MS, PhD, PCS, C/NDT is a board-certified clinical specialist in pediatric physical therapy. She has dedicated her career to teaching, research in childhood-onset neuromusculoskeletal disorders, and to the lifelong treatment of people with childhood-onset neurological and neuromuscular disorders such as cerebral palsy, traumatic brain injury, Duchenne muscular dystrophy, spinal muscular atrophy, Pompe disease, myelodysplasia, juvenile rheumatoid arthritis, and brachial plexus injury.

She has been involved in numerous clinical trials for the treatment of disorders including Pompe disease and other metabolic disorders, cerebral palsy, Duchenne muscular dystrophy, and spinal muscular atrophy. Dr. Case has participated in the development of international guidelines for the management of Duchenne muscular dystrophy, Pompe disease, and other glycogen storage diseases.

She teaches and consults internationally, has worked on a number of Center for Disease Control (CDC) task forces, has served on numerous committees and task forces in the pediatric section of APTA, served two terms as NC State Representative to the APTA Section on Pediatrics, and is a member of the North American Pompe Registry Board of Advisors.

I am an Associate Professor in the Department of Pediatrics, Division of Medical Genetics at Duke University; pursuing a career in clinical/translational research with 70% protected time for research. My clinical background is broad encompassing residency and fellowship training in internal medicine, endocrinology, diabetes, nutrition, metabolism, and clinical and biochemical genetics. This uniquely positioned me to evaluate and study pediatric and adult patients with inborn errors of metabolism, mitochondrial disorders, and lysosomal storage diseases. I transitioned from clinical medicine to a career in translational research to address the needs of patients with rare inherited metabolic disorders due to the paucity of therapies and biomarkers. My strength comes from my experience in managing patients with different inborn errors of metabolism and optimizing their treatment based on their underlying clinical, molecular, and biochemical phenotypes. In the era of precision medicine and big data analysis, my aim is to utilize my clinical skills and available tools at Duke University to conduct studies with implications for new drug, mechanism, and biomarker discovery. Studies are and will be conducted at Duke clinical research center in collaboration with clinical and basic scientists including Priya Kishnani, MD, Dwight Koeberl MD, Ph.D., and Karl-Dimiter Bissig MD, Ph.D. who are well established and funded clinical and basic science investigators at Duke. This collaboration allows me to integrate clinical data generated from natural history studies, with result from animal models, and metabolomics. This has implications for discovering innovative therapies, mechanisms, and biomarkers that serve and optimize patient care. I am currently analyzing metabolomics data on patients with Glycogen storage diseases and new therapeutics. I hold an IND on a PI initiated (industry-funded) clinical trial (pilot study) for using triheptanoin an anaplerotic compound that promotes energy through the Krebs cycle in patients with glycogen storage disease type 1.

• Hepatitis C 
• Primary sclerosing cholangitis
• Cirrhosis
• Liver Transplantation
• Clinical Trials
• Healthcare disparities in liver disease 
• Outcomes Research

RESEARCH INTERESTS

A multidisciplinary approach to care of individuals with genetic disorders in conjunction with clinical and bench research that contributes to:
1) An understanding of the natural history and delineation of long term complications of genetic disorders  with a special focus on liver Glycogen storage disorders, lysosomal disorders with a special focus on Pompe disease, Down syndrome and hypophosphatasia
2) ) The development of new therapies such as AAV gene therapy, enzyme therapy, small molecule and other approaches for genetic disorders through translational research

3) The development and execution of large multicenter trials to confirm safety and efficacy of potential therapies
4) Role of antibodies/immune response in patients on therapeutic proteins and AAV gene therapy

. Glycogen Storage Disease (GSD): We are actively following subjects with all types of Glycogen Storage Disease, with particular emphasis on types I, II, III, IV, VI and IX. The goal of the treatment team is to better determine the clinical phenotype and long term complications of these diseases. Attention to disease manifestations observed in adulthood, such as adenomas and risk for HCC, is of paramount importance in monitoring and treating these chronic illnesses. We are establishing clinical algorithms for managing adenomas, and the overall management of these patients including cardiac, bone, muscle and liver issues. A special focus is biomarker discovery, an Omics approach including metabolomics and immune phenotyping. We are working on AAV gene therapy for several hepatic GSDs

.Lysosomal Storage Disease: The Duke Lysosomal Storage Disease (LSD) treatment center follows and treats patients with Pompe, Gaucher, Fabry, Mucopolysaccharidosis, Niemann Pick, LAL-D and other LSD's. The Duke Metabolism Clinical Research Team is exploring many aspects of enzyme replacement therapy (ERT), including impact on different systems, differential response, and long term effects. Other symptomatic and treatment interventions for this category of diseases are also being explored in the context of clinical care.

. Pompe Disease: The care team has extensive experience in the care of infants and adults with Pompe disease and was instrumental in conducting clinical trials and the bench to bedside work that led to the 2006 FDA approval of alglucosidase alfa, the first treatment for this devastating disease. We are currently focusing on role of antibodies/immune response on patient outcome and role of immune modulation/immune suppression as an adjunct to ERT. Our team is also working on AAV gene therapy for Pompe disease. A focus is on newborn screening (NBS) and understanding the clinical phenotype and management approaches for babies identified via NBS

.  Hypophosphatasia: We follow a large cohort of patients with HPP. The goal is to understand the features of the disease beyond bone disease, development of biomarkers, role of ERT and immune responses in HPP

. Neuromuscular disorders: We are collaborating with neurologists, cardiologists and neuromuscular physicians to serve as a treatment site for clinical trials in these diseases. We are currently involved in trials of DMD and are working closely on setting up collaborations for studies in SMA.