Bone Health Assessment in Patients with Methylmalonic Acidemia

Abstract Background Methylmalonic acidemia (MMA) is a genetically heterogeneous disorder of methylmalonate and cobalamin metabolism. Isolated MMA is a rare inherited disorder of organic acid metabolism associated with elevated methylmalonic acid concentration in the blood and urine without elevation of homocysteine level or malonic acid. 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 the life-long protein restricted diet in addition to accumulation of acids and toxic metabolites in those patients. Aim of the Study To investigate the effect of restricted and modified diet on bone health in a sample of patients with MMA. Subject and Methods Clinical, nutritional, selected laboratory parameters of bone health and bone mineral density (BMD) assessment by Dual-energy X-ray absorptiometry (DXA) scan of bones were carried out on Egyptian MMA patients from Genetics Clinic, Medical Genetic Department, Ain Shams University. Bone formation was assessed by measurement of serum osteocalcin level while bone resorption was evaluated by serum carboxy terminal telopeptide of collagen type 1 (S-CTX). Results The study included 24 patients from 14 families (13 males and 11 females). Their ages ranged between 5.2 to 26 years with median age of 10 years (IQR: 6.5-14). Consanguineous marriage was present in 91.67 of families. Median age of symptoms was 140 days (IQR: 3.5-332.5) while median age of diagnosis was 12 months (IQR (2.5-40). History of fractures was present in 5 patients (20.83%). Decreased total body BMD was detected in 14 patients (54.5 %) with mean Z score of -1.31 ± 1.38 SD. Decreased spine BMD was present in 21 patients (79.16%) with mean Z score of -1.9 ± 1.1 SD. This decrease was significantly related to non-compliance, chronic acidosis, low serum copper. There was no significant relation between BMD and creatinine, calcium, vitamin D, zinc, selenium, osteocalcin or S-CTX levels. Conclusion MMA patients have decreased BMD related to copper deficiency, poor compliance and chronic acidosis. This resulted in defective bone formation and increased bone resorption.