Early Osteoporosis in RYR1-Related Central Core Disease

Abstract Background: Central core disease(CDC) is a congenital neuromuscular myopathy with a wide range of phenotypic presentations, ranging from delayed motor development, frequent falls, and difficulty maintaining posture. CDC is a rare presentation of RYR1 (Calcium release channel gene) mutation, which is also linked with the etiology of malignant hyperthermia. Clinical Case: We present a case of a 57-year-old woman who was diagnosed with osteoporosis at age of 52 with a T score of -2.3 after she had a fragility fracture of the knee. She suffered from multiple falls from poor balance. Her most recent DXA bone density scan from December of 2018 showed a T score of -2.6. On genetic testing, she was found to have a RYR1 heterozygous mutation, on exon 28.c.3800C to G(p.P1267 Arg). This sequence change led to the replacement of proline with arginine at codon 1267 of RyR1 protein. None of her immediate and extended family members showed any signs of CDC. We assume that the loss of sufficient muscle strain on bone and the catabolic effect of RYR1 myopathy are major causes of osteoporosis in our patient, although menopause, personal history of smoking, and alcohol intake could also be contributing factors. Teriparatide along with daily Calcium and Vitamin-D was prescribed. Later on, denosumab injection was also added to the regimen. The patient still has at least one episode of unprovoked fall in a month, but luckily she has not had any more fractures. Conclusion: To our knowledge, this is the first case where early osteoporosis in RYR1 myopathy has been reported.