Study title: bone health in patients with isolated methylmalonic acidemia

Abstract

Abstract Background Isolated Methylmalonic acidaemia (MMA) is a rare inherited metabolic disorder. Nutritional intervention for MMA patients includes dietary restriction of proteins along with medical food and dietary supplements. Decreased bone mineral density (BMD) is a widely accepted complication of protein restricted diet and accumulation of acids and toxic metabolites. Aim of the study To assess bone health in patients with isolated MMA and investigate the contributing factors. Patients and methods The study included all patients biochemically confirmed with isolated MMA above the age of 5 years. Clinical, dietary, and biochemical data were systematically collected. Patient compliance was assessed using author-derived score. Bone mineral density (BMD) was evaluated using dual-energy X-ray absorptiometry (DXA). Bone formation was assessed using serum osteocalcin level, while bone resorption was evaluated using carboxy-terminal telopeptide of collagen type 1 (S-CTX) in addition to selected other bone health laboratory parameters. Results The study included 24 patients. A history of fractures was present in 5 patients (20.83%). Decreased total body BMD was found in 14 patients (54.5 %) with a mean Z score of -1.31 ± 1.38 SD. Decreased spine BMD was present in 21 patients (79.16%) with a mean Z score of -1.9 ± 1.1 SD. This decrease was significantly related to non-compliance, chronic acidosis, disease severity, and low serum copper. There was no significant relation between BMD and creatinine, calcium, vitamin D, zinc, selenium, osteocalcin, or S-CTX levels. Conclusion Isolated MMA patients have defective bone formation and increased bone resorption manifested by decreased BMD and related to poor compliance, chronic acidosis, disease severity and copper deficiency.