Fractures in children with Pompe disease: a potential long-term complication.

BACKGROUND: Pompe disease (glycogen storage disease type II or acid maltase deficiency) is an autosomal recessive disorder caused by deficiency of the lysosomal enzyme acid alpha-glucosidase (GAA). Classic infantile-onset disease, characterized by cardiomegaly and profound weakness, leads to death in the first year of life from cardiorespiratory failure. Reversal of cardiomyopathy and improved motor function have been shown in clinical trials of rhGAA enzyme replacement therapy (ERT) with alglucosidase alfa (Myozyme), recently approved for clinical use. Increased survival potentially unmasks long-term complications of this previously lethal disease, including risk of skeletal fracture, recently identified at our institution and not previously reported in children with Pompe disease. OBJECTIVE: To report the risk of fracture in children with Pompe disease with increased survival with ERT. MATERIALS AND METHODS: We present four cases of fracture in patients with classic infantile Pompe disease treated with ERT at our institution, and review a study database for additional reports of fracture in this population. RESULTS: We review 19 fractures in 14 children with Pompe disease on ERT. CONCLUSION: Radiologists should be familiar with and vigilant for the association of fractures and increased survival on ERT in children with Pompe disease. We discuss potential mechanisms, implications for radiographic surveillance, potential intervention, and needs for further research.

Duke Scholars

Author Laura Elizabeth Case Orthopaedic Surgery, Physical Therapy

Author Donald Paul Frush Radiology, Pediatric Radiology

Author Thomas Joseph Weber Medicine, Endocrinology, Metabolism, and Nutrition

Author Yuan-Tsong Chen Pediatrics, Medical Genetics

Author Priya Sunil Kishnani Pediatrics, Medical Genetics