The natural history of glycogen storage disease types VI and IX: Long-term outcome from the largest metabolic center in Canada

• 21 patients with GSD-VI and -IX reporting on the natural history and treatment outcomes
• 16 novel pathogenic mutations in the PHKA2, PHKB, PHKG2 and PYGL genes
• First time to report likely liver adenoma on liver ultrasound in patients with GSD-VI
• First time to report liver fibrosis on liver biopsy specimens in patients with GSD-VI
• First time to report mild cardiomyopathy on echocardiography in patients with GSD-VI and -IXb

ObjectivesGlycogen storage disease (GSD) types VI and IX are caused by phosphorylase system deficiencies. To evaluate the natural history and long-term treatment outcome of the patients with GSD-VI and -IX, we performed an observational retrospective case study of 21 patients with confirmed diagnosis of GSD-VI or -IX.MethodsAll patients with GSD-VI or -IX, diagnosed at The Hospital for Sick Children, were included. Electronic and paper charts were reviewed for clinical features, biochemical investigations, molecular genetic testing, diagnostic imaging, long-term outcome and treatment by two independent research team members. All information was entered into an Excel database.ResultsWe report on the natural history and treatment outcomes of the 21 patients with GSD-VI and -IX and 16 novel pathogenic mutations in the PHKA2, PHKB, PHKG2 and PYGL genes. We report for the first time likely liver adenoma on liver ultrasound and liver fibrosis on liver biopsy specimens in patients with GSD-VI and mild cardiomyopathy on echocardiography in patients with GSD-VI and -IXb.ConclusionWe recommend close monitoring in all patients with GSD-VI and -IX for the long-term liver and cardiac complications. There is a need for future studies if uncooked cornstarch and high protein diet would be able to prevent long-term complications of GSD-VI and -IX.