Bone disease and osteoporosis associated with Pompe disease

Pompe disease is a lysosomal storage disorder defined by a mutation in the GAA gene encoding alpha-1,4-glucosidase alpha (acid maltase). Pompe disease encompasses a range of clinical presentations that are broadly characterized as either classic infantile Pompe disease or late-onset Pompe disease (LOPD). LOPD is a milder manifestation of the disease that presents after the first year of life and is typically characterized by mild proximal muscle weakness and lack of cardiac involvement compared to the classic infantile form. The mainstay of treatment is enzyme replacement therapy (EnRT). Decreased bone mineral density (BMD) is frequently encountered in LOPD. While bone loss is thought to be due to mechanical unloading secondary to the progressive muscle weakness associated with the disease, there is a lack of tissue-level data in support of this mechanism. We describe a 60-yr-old female with LOPD managed with EnRT who presented with proximal muscle weakness and decreased BMD on dual-energy X-ray absorptiometry. Undecalcified bone histology showed low turnover osteoporosis, and treatment was initiated with romosozumab. Romosozumab specifically may provide a promising osteoporosis therapy for LOPD-associated osteoporosis. As a sclerostin inhibitor, it both inhibits bone resorption and promotes new bone formation. We additionally emphasize that bone biopsy should be considered as a useful diagnostic tool in the evaluation of osteoporosis associated with uncommon pathologies, since bone histology provides more specific tissue-level information over clinical and laboratory evaluation as well as substantive guidance for treatment.